Amide derivatives

ABSTRACT

A compound represented by the following general formula (I):  
                 
 
     wherein X represents R 1 (R 2 )R 3 )C- where R 1  represents a C 3 -C 8  cycloalkyl group, an optionally substituted C 6 -C 14  aryl group, an optionally substituted heterocyclic residue, an optionally substituted C 6 -C 14  aryloxy group, or an optionally substituted C 7 -C 15  arylmethyl group; R 2  and R 3  independently represent hydrogen atom or a C 1 -C 5  alkyl group, or R 2  and R 3  may combine to represent a C 2 -C 7  alkylene group; or  
     X represents R 7 -A- wherein R 7  represents (i) a C1-C10 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group, an optionally substituted fluorenyl group or an optionally substituted heterocyclic group, (ii) an optionally substituted C6-C14 aryl group or (iii) an optionally substituted heterocyclic group, and A represents an oxygen atom or -N-R 8  where R 8  represents hydrogen atom or a C1-C5 alkyl group.  
     Y represents an oxygen atom or a sulfur atom,  
     R 4  and R 5  independently represent hydrogen atom or a C 1 -C 5  alkyl group; and R 6  represents hydrogen atom, a C 1 -C 5  alkyl group which may optionally be substituted with a hydroxyl group, a hydroxyl group or a C 1 -C 5  alkoxy group,  
     provided that the compounds wherein R 7  is a benzyl group, A and Y are an oxygen atom, R 4  and R 5  are hydrogen atom, and R 6  is a propyl group are excluded, or a salt thereof, or a solvate thereof or a hydrate thereof.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is a divisional application of U.S. application Ser. No. 09/469,354 filed Dec. 22, 1999 which is a continuation-in-part of U.S. application Ser. No. 09/103,500, filed Jun. 24, 1998, the disclosures of which are expressly incorporated by reference herein in their entireties.

TECHNICAL FIELD

[0002] The present invention relates to novel amide derivatives having strong antibacterial activity against Helicobacter pylori.

BACKGROUND ART

[0003]Helicobacter pylori is a slightly aerobic gram-negative bacterium which was recently isolated from human gastric mucosa, and various published reports suggest its involvement in inflammation of alimentary tract, formation and recurrence of ulcer, and moreover, gastric cancer (Molecular Medicine, Vol. 31, pp.1304-1374, 1994).

[0004] For the treatment of gastrointestinal ulcers, medicaments such as H₂ blockers or proton-pump inhibitors have been used so far. Since relation between Helicobacter pylori infection and gastric ulcer has been being clarified as explained above, an antibacterial agent such as amoxicillin has become practically used in combination, particularly from a viewpoint of prevention of recurrence. However, in most cases, ordinarily used antibacterial agents fail to achieve complete elimination of the bacteria. In addition, they may affect on intestinal bacterial flora due to their broad antibacterial spectra, and they often cause adverse effects such as diarrhea. Therefore, it has been desired to develop an antibacterial agent having potent antibacterial activity in alimentary tract that is specific against Helicobacter pylori.

[0005] The compound represented by the general formula (I) defined herein below wherein R⁷ is a benzyl group, and A and Y are an oxygen atom, and R⁴ and R⁵ are a hydrogen atom, and R⁶ is a propyl group, has been reported as intermediates of receptor models (Journal of American Chemical Society, Vol.115, pp.3548, 1993). However, it has not been known that this compound has an antibacterial activity against Helicobacter pylori.

DISCLOSURE OF THE INVENTION

[0006] The inventors of the present invention conducted researches to provide a novel anti-Helicobacter pylori agent, and as a result, they found that the compounds represented by the following general formula have excellent antibacterial activity against Helicobacter pylori, and can exhibit potent antibacterial activity in alimentary tract. The present invention was achieved on the bas of these findings.

[0007] The present invention thus provides amide derivatives represented by the following general formula (I) and salts thereof and solvates thereof and hydrates thereof:

[0008] wherein X represents R¹(R²)(R³)C- where R¹ represents a C₃-C₈ cycloalkyl group, an optionally substituted C₆-C₁₄ aryl group, an optionally substituted heterocyclic residue wherein the heterocyclic residue is one of furan ring, dihydrofuran ring, tetrahydrofuran ring, pyran ring, dihydropyran ring, tetrahydropyran ring, bexizofuran ring, dihydrobenzofuran ring, isobenzofuran ring, chromene ring, chroman ring, isochroman ring, thiophene ring, benzothiophene ring, pyrrole ring, pyrroline ring, pyrrolidine ring, imidazole ring, imidazoline ring, imidazolidine ring, pyrazole ring, pyrazoline ring, pyrazolidine ring, triazole ring, tetrazole ring, pyridine ring, pyridineoxide ring, piperidine ring, pyrazine ring, piperazine ring, pyrimidine ring, pyridazine ring, indolizine ring, indole ring, indoline ring, isoindole ring, isoindoline ring, indazole ring, benzinidazole ring, purine ring, quinolizine ring, quinoline ring, phthalazine ring, naphthylidine ring, quinoxaline ring, quinazoline ring, cinnoline ring, pteridine ring, oxazole ring, oxazolidine ring, isoxazole ring, isoxazolidine ring, thiazole ring, thiazylidine ring, isothiazole ring, isothiazolidine ring, dioxane ring, dithian ring, morpholine ring, and thiomorpholine ring, an optionally substituted C₆-C₁₄ aryloxy group, or an optionally substituted C₇-C₁₅ arylmethyl group; R² and R³ independently represent hydrogen atom or a C₁-C₅ alkyl group, or R² and R³ may combine to represent a C₂-C₇ alkylene group; or

[0009] X represents R⁷A- wherein R⁷ represents (i) a C1-C10 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group, an optionally substituted fluorenyl group or an optionally substituted heterocyclic group, (ii) an optionally substituted C6-C14 aryl group or (iii) an optionally substituted heterocyclic group, and A represents an oxygen atom or -N-R⁸ where R⁶ represents hydrogen atom or a C1-C5 alkyl group,

[0010] Y represents an oxygen atom or a sulfur atom,

[0011] R⁴ and R⁵ independently represent hydrogen atom or a C₁-C₅ alkyl group; and R⁶ represents hydrogen atom, a C₁-C₅ alkyl group which may optionally be substituted with a hydroxyl group, a hydroxyl group or a C₁-C₅ alkoxy group,

[0012] provided that the compounds wherein R⁷ is a benzyl group, A and Y are an oxygen atom, R⁴ and R⁵ are hydrogen atom, and R⁶ is a propyl group are excluded, or a salt thereof, or a solvate thereof or a hydrate thereof.

[0013] According to another aspect of the present invention, the present invention provides medicaments, preferably for the treatment of gastric diseases, e.g., gastritis, gastric ulcer, and gastric cancer, which comprise as an active ingredient a subs selected from the group consisting of the aforementioned amide derivatives and pharmaceutically acceptable salts thereof, and solvates thereof and hydrates thereof. The medicaments are preferably provided as pharmaceutical compositions comprising the aforementioned substance as an active ingredient together with one or more pharmaceutically acceptable additives. These medicaments can be used as anti-Helicobacter pylori agents for therapeutic and/or preventive treatment of digestive diseases related to Helicobacter pylori infection, for example, gastritis, gastric ulcer, gastric cancer, stomach malignant lymphoma, MALT lymphoma, duodenal ulcer, duodenal carcinoma and the like.

[0014] According to further aspects of the present invention, there are provided a method for treating digestive diseases related to Helicobacter pylori infection which comprises the step of administering to a mammal including a human a therapeutically effective amount of a substance selected from the group consisting of the aforementioned amide derivatives and pharmaceutically acceptable salts thereof, and solvates thereof and hydrates thereof, and a use of a substance selected from the group consisting of the aforementioned amide derivatives and pharmaceutically acceptable salts thereof, and solvates thereof and hydrates thereof for the manufacture of the above medicaments.

BEST MODE FOR CARRYING OUT THE INVENTION

[0015] In the general formula (I), examples of the C₃-C₈ cycloalkyl group represented by R¹ include, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, and cyclooctyl group. Examples of the C₆-C₁₄ aryl group include, for example, aromatic hydrocarbon groups consisting of one ring or two to approximately three condensed aromatic rings such as phenyl group, naphthyl group, and anthryl group.

[0016] As the residue of a heterocyclic compound, residues of heterocyclic compounds containing 1 to 4 heteroatoms selected from oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-membered atoms in total can be used. More specifically, examples of the residues of heterocyclic compounds include, for example, furan ring, dihydrofuran ring, tetrahydrofuran ring, pyran ring, dihydropyran ring, tetrahydropyran ring, benzofuran ring, dihydiobenzofuran ring, isobenzofuran ring, chromene ring, chroman ring, isochroman ring, thiophene ring, benzothiophene ring, pyrrole ring, pyrroline ring, pyrrolidine ring, imidazole ring, imidazoline ring, imidazolidine ring, pyrazole ring, pyrazoline ring, pyrazolidine ring, triazole ring, tetrazole ring, pyridine ring, pyridineoxide ring, piperidine ring, pyrazine ring, piperazine ring, pyrimidine ring, pyridazine ring, indolizine ring, indole ring, indoline ring, isoindole ring, isoindoline ring, indazole ring, benzimidazole ring, purine ring, quinolizine ring, quinoline ring, phthalazine ring, naphthylidine ring, quinoxaline ring, quinazoline ring, cinnoline ring, pteridine ring, oxazole ring, oxazolidine ring, isoxazole ring, isoxazolidine ring, thiazole ring, thiazylidine ring, isothiazole ring, isothiazoline ring, dioxane ring, dithian ring, morpholine ring, and thiomorpholine ring. Examples of the C₅-C₁₄ aryloxy group include, for example, phenyloxy group, naphthyloxy group, and anthryloxy group, and examples of the C₇-C₁₅ arylmethyl group include, for example, benzyl group, naphthylmethyl group, and anthrylmethyl group.

[0017] The C₁-C₅ alkyl group independently represented by R² and R³ may be either a straight-or branched-chain alkyl, and examples include, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, and isopentyl group. Examples of the C₂-C₇ alkylene group represented by R² combined with R³ include, for example, ethylene group, trimethylene group, tetramethylene group, pentamethylene group, bexamethylene group, and heptamethylene group, and these groups may have one or more branched chains.

[0018] As the C₁-C₅ alkyl group represented by R⁴ and R⁵, those explained for R² and R³ can be independently used. In the present invention, R⁴ and R⁵ are preferably hydrogen atom.

[0019] As the C₁-C₅ alkyl group represented by R⁶, those explained for R² and R³ can be used, and these alkyl groups may be substituted with at least one, preferably one hydroxy group. The C₁-C₅ alkoxy group represented by R⁶ may be a straight or branched chain group, and examples include, for example, methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, tert-butoxy group, pentyloxy group, and isopentyloxy group. In the present invention, R⁶ is preferably an alkyl group, more preferably a methyl group.

[0020] As the C₁-C₁₀ alkyl group represented by R⁷ in the general formula (I) above, those having a straight or branched chain can be used, and examples include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, isopentyl group, hexyl group, isohexyl group, heptyl group, octyl group, nonyl group, and decyl group. These alkyl groups may optionally be substituted with a C₆-C₁₄ aryl group, a fluorenyl group or a heterocyclic group. The C₆-C₁₄ aryl group which can be a substituent on the alkyl group represented by R⁷ includes, for example, a C₆-C₁₄ aryl group such as phenyl group, naphtyl group or anthryl group. The heterocyclic group which can be a substituent on the alkyl group represented by R⁷ includes, for example, those described for R¹.

[0021] As the C₆-C₁₄ aryl group and the heterocyclic group represented by R⁷, those described for the substituent on the C₁-C₁₀ alkyl group can be used.

[0022] R⁷ is preferably a C₁-C₁₀ alkyl group which may optionally be substituted with an optionally substituted C₆-C₁₄ aryl group or an optionally substituted heterocyclic group, more preferably a C₁-C₅ alkyl group which may optionally be substituted with an optionally substituted C₆-C₁₄ aryl group or an optionally substituted heterocyclic group, still more preferably a methyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group. In the present invention, R⁷ is particularly preferably a methyl group which is substituted with an optionally substituted C₆-C₁₄ aryl group or a methyl group which is substituted with an optionally substituted heterocyclic group.

[0023] A represents an oxygen atom or -N-R⁸ wherein R⁸ represents hydrogen atom or a C₁-C₅ alkyl group. The C₁-C₅ alkyl group represented by R⁸ includes methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, and isopentyl group. A is preferably an oxygen atom or -N-H.

[0024] Y represents an oxygen atom or a sulfur atom. Y is preferably an oxygen atom.

[0025] The aforementioned aryl group, residue of a heterocyclic compound, aryloxy group, and arylmethyl group may have one or more substituents at arbitrary positions on their rings. Examples of substituents include, for example, a halogen atom such as fluorine atom, chlorine atom, and bromine atom; a C₁-C₅ alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, and tert-pentyl group; a C₇-C₁₅ aralkyl group such as benzyl group, phenylethyl group, and naphthylmethyl group; trifluoromethyl group; a C₇-C₁₅ alkoxy group such as methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, tert-butoxy group, pentyloxy group, and isopentyloxy group; a C₇-C₁₅ aralkyloxy group such as benzyloxy group, phenylethyloxy group, and naphthylmethyloxy group; a C₁-C₅ alkylenedioxy group such as methylenedioxy group, ethylenedioxy group, and propylenedioxy group; hydroxy group; nitro group; a C₂-C₆ alkylcarbonyloxy group such as acetoxy group, propionyloxy group, butyryloxy group, and valeryloxy group; carboxyl group; a C₂-C₆ alkoxycarbonyl group such as methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, isobutoxycarbonyl group, tertbutoxycarbonyl group, and pentyloxycarbonyl group; a C₇-C₁₆ aralkyloxycarbonyl group such as benzyloxycarbonyl group, phenylethyloxycarbonyl group, and naphthylmethyloxycarbonyl group; oxo group; a C₂-C₆ alkylcarbonyl group such as acetyl group, propioxyl group, butyryl group, and valeryl group; amino group; a C₁-C₅ monoalkylamino group such as methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, tert-butylamino group, pentylamino group, and isopentylamino group; a C₂-C₁₀ dialkylamino group such as dimethylamino group, ethylmethylamino group, diethylamino group, methylpropylamino group, and diisopropylamino group; a C₂-C₆ alkylcarbonylamimno group such as acetylamino group, propionylamino group, isopropionylamino group, butyrylamino group, and valerylamino group; a C₂-C₆ alkoxycarbonylamino group such as methoxycarbonylamino group, ethoxycarbonylamino group, propoxycarbonylamino group, isopropoxycarbonylamino group, butoxycarbonylamino group, isobutoxycarbonylamino group, tert-butoxycarbonylamino group, and pentyloxycarbonylamino group; a C₇-C₁₅ aralkyloxycarbonylamino group such as benzyloxycarbonylamino group, phenylethyloxycarbonylamino group, and naphthylmethyloxycarbonylamino group; carbamoyl group; a C₂-C₆ alkylcarbamoyl group such as methylcarbamoyl group, ethylcarbamoyl group, propylcarbamoyl group, butylcarbamoyl group, tert-butylcarbamoyl group, and pentylcarbamoyl group; a C₆-C₁₂ aryl group such as phenyl group, and naphthyl group and the like.

[0026] Among the compounds of the present invention represented by the above formula (I) wherein X is R¹(R²)(R³)C-, preferred compounds include those wherein R¹ is a C₆-C₁₄ aryl group which may optionally be substituted, a residue of a heterocyclic compound which may optionally be substituted, a C₆-C₁₄ aryloxy group which may optionally be substituted, or a C₇-C₁₅ arylmethyl group which may optionally be substituted, R², R³, R⁴ and R⁵ are hydrogen atoms, R⁶ is a C₁-C₆ alkyl group, and Y is an oxygen atom. More preferred compounds include those wherein R¹ is a C₆-C₁₄ aryl group which may optionally be substituted, a residue of a heterocyclic compound which may optionally be substituted, a C₆-C₁₄ aryloxy group which may optionally be substituted, or a C₇-C₁₅ arylmethyl group which may optionally be substituted, R², R³, R⁴ and R⁵ are hydrogen atoms, R⁶ is methyl group, and Y is an oxygen atom.

[0027] Examples of particularly preferred compounds include:

[0028] N-(3-methylcarbamoylphenyl)-3-chlorophenylacetamide;

[0029] N-(3-methylcarbamoylphenyl)-4-chlorophenylacetamide,;

[0030] N-(3-methylcarbamoylphenyl)-3-bromophenylacetamide;

[0031] N-(3-methylcarbamoylphenyl)-4-bromophenylacetamide;

[0032] N-(3-methylcarbamoylphenyl)-3-methylphenylacetamide;

[0033] N-(3-methylcarbamoylphenyl)-4-methylphenylacetamide;

[0034] N-(3-methylcarbamoylphenyl)-3-methoxyphenylacetamide;

[0035] N-(3-methylcarbamoylphenyl)-4-methoxyphenylacetamide;

[0036] N-(3-methylcarbamoylphenyl)-3,4,5-trimethoxyphenylacetamide;

[0037] N-(3-methylcarbamoylphenyl)-3-benzyloxyphenylacetamide;

[0038] N-(3-methylcarbamoylphenyl)-1-naphthylacetamide;

[0039] N-(3-methylcarbamoylphenyl)-2-naphthylacetamide;

[0040] N-(3-methylcarbamoylphenyl)-3-indoly)acetamide;

[0041] N-(3-methylcarbamoylphenyl)-3-benzothienylacetamide;

[0042] N-(3-methylcarbamoylphenyl)-4-benzothienylacetamide;

[0043] N-(3-methylcarbamoylphenyl)-3,4-methylenedioxyphenylacetamide;

[0044] N-(3-methylcarbamoylphenyl)-2-chlorophenoxyacetamide;

[0045] N-(3-methylcarbamoylphenyl)-2,3-dichlorophenoxyacetamide;

[0046] N-(3-methylcarbamoylphenyl)-1-naphthyloxyacetide;

[0047] N-(3-methylcarbamoylphenyl)-2-naphthyloxyacetamide; and

[0048] N-(3-methylcarbamoylphenyl-3-(2-methoxyphenyl)propionamide.

[0049] Among the compounds of the above formula (I) wherein X is R⁷-A-, preferred compounds include those wherein R⁴ and R⁵ are hydrogen atom, A is an oxygen atom or -N-H and Y is an oxygen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof. More preferred compounds include those wherein R⁷ is a methyl group which is substituted with an optionally substituted C₆-C₄ aryl group or heterocyclic group, R⁴ and R⁵ are hydrogen atom, R⁶ is a methyl group, A is an oxygen atom or -N-H and Y is an oxygen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

[0050] Particularly preferred compounds include a compound selected from the group consisting of:

[0051] N′-methyl-3-(2-chlorobenzyloxycarbonylamino)benzamide;

[0052] N′-methyl-3-(4-chlorobenzyloxycarbonylamino)benzamide;

[0053] N′-methyl-3-(2,3-dichlorobenzyloxycarbonylamino)benzamide;

[0054] N′methyl-3-(2,6-dichlorobenzyloxycarbonylamino)benzamide;

[0055] N′-methyl-3-(2-bromobenzyloxycarbonylamino)benzamide;

[0056] N′-methyl-3(2-methylbenzyloxycarbonylamino)benzamide;

[0057] N′-methyl-3-(3-methylbenzyloxycarbonylamino)benzamide;

[0058] N-methyl-3-(4-methylbenzyloxycarbonylamino)benzamide;

[0059] N′-methyl-3-(1-naphthylmethoxycarbonylamino)benzamide; and

[0060] N′-methyl-3-(2-naphthylmethoxycarbonylmino)benzamide;

[0061] or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

[0062] The amide derivatives of the present invention represented by the above general formula (I) can form a salt. Where one or more acidic groups exist examples of salts include, for example, metal sats such as lithium salt, sodium salt, potassium salt, magnesium salt, and calcium salt, and ammonium salts such as inorganic ammonium salt, methylammonium salt, dimethylammonium salt, trimethylammonium salt, and dicyclohexylammonium salt. Where one or more basic groups exist, examples of salts include, for example, mineral acid salts such as hydrochloride, hydrobromide, sulfate, nitrate, and phosphate, and organic acid salts such as methanesulfonate, benzenesulfonate, p-toluenesulfonate, acetate, propionate, tartrate, fumarate, maleate, malate, oxalate, succinate, citrate, benzoate, mandelate, cinnamate, and lactate. Pharmaceutically acceptable salts are preferred as the active ingredient of the medicaments of the present invention. The amide derivatives of the present invention represented by the above general formula (I) and salts thereof may also exist as solvates or hydrates. Any substances in the form of salts, solvates, or hydrates as well as compounds in free forms fall within the scope of the present invention.

[0063] As to the stereochemistry of asymmetric carbon atoms present in the amide derivatives of the present invention represented by the general formula (I), the atoms can independently be in (S), (R), or (RS) configuration. Isomers in pure forms based on one or more asymmetric carbon atoms, e.g., enantiomers and diastereoisomers, any mixtures of such isomers, racemates and the like fall within the scope of the present invention.

[0064] Examples of specific examples of the amide derivatives of the present invention represented by the above general formula (I) wherein X is R¹(R²)(R³)C-, and Y is an oxygen atom, include those listed in Table 1. TABLE 1 Compd. No. R¹ R² R³ R⁴ R⁵ R⁶ 1

H H H H CH₃ 2

H H H H CH₃ 3

H H H H CH₃ 4

H H H H CH₃ 5

H H H H CH₃ 6

H H H H CH₃ 7

H H H H CH₃ 8

CH₃ H H H CH₃ 9

CH₃ CH₃ H H CH₃ 10

CH₃ CH₃ CH₃ H CH₃ 11

—(CH₂)₄— H H CH₃ 12

—(CH₂)₅— H H CH₃ 13

H H H H CH₃ 14

H H H H CH₃ 15

H H H H CH₃ 16

H H H H CH₃ 17

H H H H CH₃ 18

H H H H CH₃ 19

H H H H CH₃ 20

H H H H H 21

H H CH₃ H CH₃ 22

H H H H CH₃ 23

H H H CH₃ CH₃ 24

H H H H CH₂CH₃ 25

H H H H CH₂CH₂CH₃ 26

H H H H (CH₂)₃CH₃ 27

H H H H (CH₂)₄CH₃ 28

H H H H CH₂CH₂OH 29

H H H H OH 30

H H H H OCH₃ 31

H H H H OCH₂CH₃ 32

H H H CH₂CH₃ CH₂CH₃ 33

H H H H CH₃ 34

H H H H CH₃ 35

H H H H CH₃ 36

H H H H CH₃ 37

H H H H CH₃ 38

H H H H CH₃ 39

H H H H CH₃ 40

H H H H CH₃ 41

H H H H CH₃ 42

H H H H CH₃ 43

H H H H CH₃ 44

H H H H CH₃ 45

H H H H CH₃ 46

H H H H CH₃ 47

H H H H CH₃ 48

H H H H CH₃ 49

H H H H CH₃ 50

H H H H CH₃ 51

H H H H CH₃ 52

H H H H CH₃ 53

H H H H CH₃ 54

H H H H CH₃ 55

H H H H CH₃ 56

H H H H CH₃ 57

H H H H CH₃ 58

H H H H CH₃ 59

H H H H CH₃ 60

H H H H CH₃ 61

H H H H CH₃ 62

H H H H CH₃ 63

H H H H CH₃ 64

H H H H CH₃ 65

H H H H CH₃ 66

H H H H CH₃ 67

H H H H CH₃ 68

H H H H CH₃ 69

H H H H CH₃ 70

H H H H CH₃ 71

H H H H H 72

H H H H CH₃ 73

H H H H CH₃ 74

H H H H CH₃ 75

H H H H CH₃ 76

H H H H CH₃ 77

H H H H CH₃ 78

H H H H CH₃ 79

H H H H CH₃ 80

H H H H CH₃ 81

H H H H CH₃ 82

H H H H CH₃ 83

H H H H CH₃ 84

H H H H CH₃ 85

H H H H CH₃ 86

H H H H CH₃ 87

H H H H CH₃ 88

H H H H CH₃ 89

H H H H CH₃ 90

H H H H CH₃ 91

H H H H CH₃ 92

H H H H CH₃ 93

H H H H CH₃ 94

H H H H CH₃ 95

H H H H CH₃ 96

H H H H CH₃ 97

H H H H CH₃ 98

H H H H CH₃ 99

H H H H CH₃ 100

H H H H CH₃ 101

H H H H CH₃ 102

H H H H CH₃ 103

H H H H CH₃ 104

H H H H CH₃ 105

H H H H CH₃ 106

H H H H CH₃ 107

H H H H CH₃ 108

H H H H CH₃ 109

H H H H CH₃ 110

H H H H CH₃ 111

H H H H CH₃ 112

H H H H CH₃ 113

H H H H CH₃ 114

H H H H CH₃ 115

H H H H CH₃ 116

H H H H CH₃ 117

H H H H CH₃ 118

H H H H CH₃ 119

H H H H CH₃ 120

H H H H CH₃ 121

H H H H CH₃ 122

H H H H CH₃ 123

H H H H CH₃ 124

H H H H CH₃ 125

H H H H CH₃ 126

H H H H CH₃ 127

H H H H CH₃ 128

H H H H CH₃ 129

H H H H CH₃ 130

H H H H CH₃ 131

H H H H CH₃ 132

H H H H CH₃ 133

H H H H CH₃ 134

H H H H CH₃ 135

H H H H CH₃ 136

H H H H CH₃ 137

H H H H CH₃ 138

H H H H CH₃ 139

H H H H CH₃ 140

H H H H CH₃ 141

H H H H CH₃ 142

H H H H CH₃ 143

H H H H CH₃ 144

H H H H CH₃ 145

H H H H CH₃ 146

H H H H CH₃ 147

H H H H CH₃ 148

H H H H CH₃ 149

H H H H CH₃ 150

H H H H CH₃ 151

H H H H CH₃ 152

H H H H CH₃ 153

H H H H CH₃ 154

H H H H CH₃ 155

H H H H CH₃ 156

CH₃ H H H CH₃ 157

CH₃ CH₃ H H CH₃ 158

H H H H CH₃ 159

H H H H CH₃ 160

H H H H CH₃ 161

H H H H CH₃ 162

H H H H CH₃ 163

H H H H CH₃ 164

H H H H CH₃ 165

H H H H CH₃ 166

H H H H CH₃ 167

H H H H CH₃ 168

H H H H CH₃ 169

H H H H CH₃ 170

H H H H CH₃ 171

H H H H CH₃ 172

H H H H CH₃ 173

H H H H CH₃ 174

H H H H CH₃ 175

H H H H CH₃ 176

H H H H CH₃ 177

H H H H CH₃ 178

H H H H CH₃ 179

H H H H CH₃ 180

H H H H CH₃ 181

H H H H CH₃ 182

H H H H CH₃ 183

H H H H CH₃ 184

H H H H CH₃ 185

H H H H CH₃ 186

H H H H CH₃ 187

H H H H CH₃ 188

H H H H CH₃ 189

H H H H CH₃ 190

H H H H CH₃ 191

H H H H CH₃ 192

H H H H CH₃ 193

H H H H CH₃ 194

H H H H CH₃ 195

H H H H CH₃ 196

H H H H CH₃ 197

H H H H CH₃ 198

H H H H CH₃ 200

H H H H CH₃ 201

H H H H CH₃ 202

H H H H CH₃ 203

H H H H CH₃ 204

H H H H CH₃ 205

H H H H CH₃ 206

H H H H CH₃ 207

H H H H CH₃ 208

H H H H CH₃ 209

H H H H CH₃ 210

H H H H CH₃ 211

H H H H CH₃ 212

H H H H CH₃ 213

H H H H CH₃ 214

H H H H CH₃ 215

H H H H CH₃ 216

H H H H CH₃ 217

H H H H CH₃ 218

H H H H CH₃ 219

H H H H CH₃ 220

H H H H CH₃ 221

H H H H CH₃ 222

H H H H CH₃ 223

H H H H CH₃ 224

H H H H CH₃ 225

H H H H CH₃ 226

H H H H CH₃ 227

H H H H CH₃ 228

H H H H CH₃ 229

H H H H CH₃ 230

H H H H CH₃ 231

H H H H CH₃ 232

H H H H CH₃ 233

H H H H CH₃ 234

H H H H CH₃ 235

H H H H CH₃ 236

H H H H CH₃ 237

H H H H CH₃ 238

H H H H CH₃ 239

H H H H CH₃ 240

H H H H CH₃ 241

H H H H CH₃ 242

H H H H CH₃ 243

H H H H CH₃ 244

H H H H CH₃ 245

H H H H CH₃ 246

H H H H CH₃ 247

H H H H CH₃ 248

H H H H CH₃ 249

H H H H CH₃ 250

H H H H CH₃ 251

H H H H CH₃ 252

H H H H CH₃

[0065] Examples of specific examples of the amide derivatives of the present invention represented by the above general formula (I) wherein X is R⁷A-, include those listed in Table 2. TABLE 2 Compd. No. R⁷ A Y R⁴ R⁵ R⁶  1 CH₃ O O H H CH₃  2 NH O  3  4  5  6

O O NH NH O S O S H H CH₃  7  8

O NH O O H H H  9  10

O NH O O H CH₃ CH₃  11  12

O NH O O H H CH₂CH₃  13  14

O NH O O H H CH₂CH₂CH₃  15  16

O NH O O CH₃ H CH₃  17  18

O NH O O H H CH₃  19  20

O NH O O H H CH₃  21  22

O NH O O H H CH₃  23  24

O NH O O H H CH₃  25  26

O NH O O H H CH₃  27  28

O NH O O H H CH₃  29  30

O NH O O H H CH₃  31  32

O NH O O H H CH₃  33  34

O NH O O H H CH₃  35  36

O NH O O H H CH₃  37  38

O NH O O H H CH₃  39  40

O NH O O H H CH₃  41  42

O NH O O H H CH₃  43  44

O NH O O H H CH₃  45  46

O NH O O H H CH₃  47  48

O NH O O H H CH₃  49  50

O NH O O H H CH₃  51  52

O NH O O H H CH₃  53  54

O NH O O H H CH₃  55  56

O NH O O H H CH₃  57  58

O NH O O H H CH₃  59  60

O NH O O H H CH₃  61  62

O NH O O H H CH₃  63  64

O NH O O H H CH₃  65  66

O NH O O H H CH₃  67  68

O NH O O H H CH₃  69  70

O NH O O H H CH₃  71  72

O NH O O H H CH₃  73  74

O NH O O H H CH₃  75  76

O NH O O H H CH₃  77  78

O NH O O H H CH₃  79  80

O NH O O H H CH₃  81  82

O NH O O H H CH₃  83  84

O NH O O H H CH₃  85  86

O NH O O H H CH₃  87  88

O NH O O H H CH₃  89  90

O NH O O H H CH₃  91  92

O NH O O H H CH₃  93  94

O NH O O H H CH₃  95  96

O NH O O H H CH₃  97  98

O NH O O H H CH₃  99 100

O NH O O H H CH₃ 101 102

O NH O O H H CH₃ 103 104

O NH O O H H CH₃ 105 106

O NH O O H H CH₃ 107 108

O NH O O H H CH₃ 109 110

O NH O O H H CH₃ 111 112

O NH O O H H CH₃ 113 114

O NH O O H H CH₃ 115 116

O NH O O H H CH₃ 117 118

O NH O O H H CH₃ 119 120

O NH O O H H CH₃ 121 122

O NH O O H H CH₃ 123 124

O NH O O H H CH₃ 125 126

O NH O O H H CH₃ 127 128

O NH O O H H CH₃ 129 130

O NH O O H H CH₃ 131 132

O NH O O H H CH₃ 133 134

O NH O O H H CH₃ 135 136

O NH O O H H CH₃ 137 138

O NH O O H H CH₃ 139 140

O NH O O H H CH₃ 141 CH₃CH₂ O O H H CH₃ 142 NH O 143 144

O NH O O H H CH₃ 145 146

O NH O O H H CH₃ 147 148

O NH O O H H CH₃ 149 150

O NH O O H H CH₃ 151 152

O NH O O H H CH₃ 153 154

O NH O O H H CH₃ 155 156

O NH O O H H CH₃ 157 158

O NH O O H H CH₃ 159 160

O NH O O H H CH₃ 161 162

O NH O O H H CH₃ 163 164

O NH O O H H CH₃ 165 166

O NH O O H H CH₃ 167 168

O NH O O H H CH₃ 169 170

O NH O O H H CH₃ 171 172

O NH O O H H CH₃ 173 174

O NH O O H H CH₃ 175 176

O NH O O H H CH₃ 177 178

O NH O O H H CH₃ 179 180

O NH O O H H CH₃ 181 182 183 184 185 186

O NH NCH₃O NH NCH₃ O O O S S S H H CH₃ 187 188

O NH O O H H H 189 190

O NH O O H CH₃ CH₃ 191 192

O NH O O H H CH₂CH₃ 193 194

O NH O O H H CH₂CH₂CH₃ 195 196

O NH O O CH₃ H CH₃ 197 198

O NH O O H H CH₃ 199 200

O NH O O H H CH₃ 201 202

O NH O O H H CH₃ 203 204

O NH O O H H CH₃ 205 206

O NH O O H H CH₃ 207 208

O NH O O H H CH₃ 209 210

O NH O O H H CH₃ 211 212

O NH O O H H CH₃ 213 214

O NH O O H H CH₃ 215 216

O NH O O H H CH₃ 217 218

O NH O O H H CH₃ 219 220

O NH O O H H CH₃ 221 222

O NH O O H H CH₃ 223 224

O NH O O H H CH₃ 225 226

O NH O O H H CH₃ 227 228

O NH O O H H CH₃ 229 230

O NH O O H H CH₃ 231 232

O NH O O H H CH₃ 233 234

O NH O O H H CH₃ 235 236

O NH O O H H CH₃ 237 238

O NH O O H H CH₃ 239 240

O NH O O H H CH₃

[0066] The amide derivatives of the present invention represented by the above general formula (I) wherein X is R¹(R²)(R³)C-, and Y is an oxygen atom, can be prepared by, for example, the method explained below.

[0067] wherein R¹, R², R³, R⁴, R⁵ and R⁶ are the same as those defined above.

[0068] A carboxylic acid derivative represented by the above general formula (II) is allowed to react with a condensing agent such as dicyclohexylcarbodiimide, diphenylphospboryl azide, carbonyldiimidazole, oxalyl chloride, isobutyl chloroformate, and thionyl chloride, optionally in the presence of a base such as triethylamine and pyridine as required, to activate a carboxylic acid, and then the resulting intermediate is allowed to react with an aniline derivative represented by the above general formula (III), optionally in the presence of a base such as triethylamine and pyridine as required, to obtain a compound represented by the above general formula (I). As a solvent used in the condensation reaction, a suitable solvent may be appropriately chosen depending on a type of a condensing agent. Reaction conditions may also be appropriately chosen so as to be suitable for a condensing agent used.

[0069] In the above series of reactions, protection and deprotection of one or more functional groups may sometimes be required. In such a case, a protective group suitable for each of the reactive functional group may be chosen, and reaction procedures can be employed according to known methods described in the literature.

[0070] The amide derivatives of the present invention represented by the above general formula (I) wherein X is R⁷-A-, can be prepared by, for example, the method explained below.

[0071] wherein R⁷, R⁴, R⁵, and R⁶ are the same as those defined above.

[0072] An alcohol derivative represented by the above general formula (IV) is dissolved in an inert solvent such as acetonitrile, methylene chloride or chloroform, and allowed to be reacted with di(n-succinimidyl)carbonate in the presence of base such as triethylamine or pyridine to obtain an asymmetric carbonate compound (V) as an intermediate. The compound (V) is then dissolved in a polar solvent such as dimethylformamide, N-methylpyrrolidone or dimethylsulfoxide, and allowed to be reacted with the aniline derivative (VI) in the presence of base such as triethylamine or pyridine to obtain the compound (VII) i.e., the compound represented by the formula (I) wherein A and Y are an oxygen atom.

[0073] wherein R⁷, R⁴, R⁵, R⁶ and Y are the same as those defined above.

[0074] The isocyanate derivative (VIII) is dissolved in an inert solvent such as acetonitrile, methylene chloride or chloroform, and allowed to be reacted with the aniline derivative (VI) to obtain the compound (IX), i.e., the compound represented by the formula (I) wherein A is -NH.

[0075] In the above series of reactions, protection and deprotection of one or more functional groups may sometimes be required. In such a case, a protective group suitable for each of the reactive functional group may be chosen, and reaction procedures can be employed according to known methods described in the literature.

[0076] The compounds of the present invention represented by the above general formula (I) have excellent antibacterial activity against Helicobacter pylori, and they can exhibit potent antibacterial activity against Helicobacter pylori in stomach. Accordingly, the medicaments of the present invention are useful for therapeutic and/or preventive treatment of various digestive diseases related to the infection caused by Helicobacter pylori, for example, a disease selected from the group consisting of gastritis, gastric ulcer, gastric cancer; gastric malignant lymphoma, MALT lymphoma, duodenal ulcer, and duodenal carcinoma. More specifically, the compounds may preferably be used as medicaments for therapeutic treatment of gastritis, gastric ulcer and duodenal ulcer; medicaments for preventive treatment of gastric ulcer, duodenal ulcer, gastric malignant lymphoma, gastric cancer, and duodenal carcinoma; and medicaments for preventive treatment of recurrence of gastric ulcer and duodenal ulcer.

[0077] As an active ingredient of the medicament of the present invention, one or more substances selected from the group consisting of the compound represented by the above general formula (I) and a pharmaceutically acceptable salt thereof, and a solvate thereof and a hydrate thereof can be used. The medicament of the present invention may preferably be provided in the form of a pharmaceutical composition comprising the above substance as an active ingredient and one or more pharmaceutically acceptable additives for pharmaceutical preparations. In the pharmaceutical compositions, a ratio of the active ingredient to the pharmaceutical additive may be about 1% by weight to about 90% by weight.

[0078] The medicament of the present invention may be administered as a pharmaceutical composition for oral administration such as granules, subtilized granules, powders, hard capsules, soft capsules, syrups, emulsions, suspensions, and liquid drugs, or administered as a pharmaceutical composition for parenteral administration such as injections for intravenous, intramuscular or subcutaneous administration, drip infusions, and suppositories. A preparation prepared as a powdery pharmaceutical composition may be dissolved before use and used as an injection or a drip infusion.

[0079] Solid or liquid pharmaceutical additives may be used for preparation of the pharmaceutical compositions. The pharmaceutical additives may be either organic or inorganic materials. Examples of excipients used for manufacturing solid preparations include, for example, lactose, sucrose, starch, talc, cellulose, dextrin, china clay, and calcium carbonate. For the manufacture of liquid formulations for oral administration such as emulsions, syrups, suspensions, and liquids, for example, ordinary inert diluents such as water and vegetable oils may be used. In addition to the inert diluents, auxiliaries such as, for example, moistening agents, suspending aids, sweetening agents, aromatics, colorants, preservatives and the like may be formulated. Liquid preparations may be filled in capsules after their preparation that are made of an absorbable material such as gelatin. Examples of solvents or suspending mediums used for the manufacture of pharmaceutical preparations for parenteral administration such as injections and suppositories include, for example, water, propylene glycol, polyethylene glycol, benzyl alcohol, ethyl oleate, lecithin and the like. Examples of base materials used for preparation of suppositories include, for example, cacao butter, emulsified cacao butter, lauric lipid, Witepsol and the like. Methods for manufacturing the pharmaceutical preparations are not particularly limited, and any methods ordinarily used in the art may be employed.

[0080] A dose of the medicament of the present invention may generally be from about 0.01 to 5,000 mg per day for an adult based on the weight of the compounds of the present invention. However, it is preferred to suitably increase or decreased depending on age, conditions, symptoms or other of a patient. The daily dose may be administered once a day or two to three times a day with suitable intervals, or alternatively, intermittently administered with intervals of several days. When used as an injection, a dose of the medicaments of the present invention may be about 0.001 to 100 mg per day for an adult based on the weight of the compounds of the present invention.

EXAMPLES

[0081] The present invention will be explained more specifically by referring to the following examples. However, the scope of the present invention is not limited to these examples.

Example 1 Preparation of N-(3-methylcarbamoylphenyl)-3-chlorophenylacetamide (Compound No. 17 in Table 1)

[0082] 3-Chlorophenylacetic acid (192 mg) was dissolved in methylene chloride (8 ml), and oxalyl chloride (0.10 ml) and one drop of dimethylformamide were added to the solution. After stirring for 1 hour at room temperature, 3-aminobenzoylmethylamide (167 mg) and pyridine (0.19 ml) were added to the reaction mixture, and then stirred at room temperature overnight. After the solvent was evaporated under reduced pressure, water (10 ml) and 2N aqueous hydrochloric acid (l ml) were added to the residue, and the deposited crystals were collected by filtration and washed with water. These crystals were dried and added in ethyl acetate (6 ml), and then the mixture was heated under reflux for ten minutes. The mixture was cooled to room temperature, and the crystals were collected by filtration and washed with ethyl acetate to obtain the desired compound (233 mg, yield 68%).

[0083] Melting point: 165-166° C.

[0084] IR (KBr, cm⁻¹): 3324, 1642, 1593, 1555.

[0085] NMR DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.68 (s, 2H), 7.25-7.42 (m, 5H), 7.48 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 8.02 (dd, J=1.8 Hz, 1.8 Hz, 1H), 8.36 (d, J=4.5 Hz, 1H), 10.31 (s, 1H).

[0086] In similar manners to the method of Example 1, compounds of Examples 2-50 were prepared. Their physicochemical properties are set out below.

Example 2 Preparation of N-(3-methylcarbamoylphenyl)cyclohexylacetamide (Compound No. 4 in Table 1)

[0087] Melting point: 183° C.

[0088] IR (KBr, cm⁻¹): 3293, 1657, 1640, 1588, 1535.

[0089] NMR (DMSO-d₆, δ): 0.99 m, 2H), 1.03-1.38 (m, 3H), 1.55-1.90 (m, 6H), 2.19 (d, J=7.0 Hz, 2 H), 2.76 (d, J=4.5 Hz, 3H), 7.34 (dd, J=7.8 Hz, 7.8 Hz, 1H, 7.45 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.34 (d, J=4.5 Hz, 1H), 9.95 (s, 1H).

Example 3 Preparation of N-(3-methylcarbamoylphenyl)phenylacetamide (Compound No. 7 in Table 1)

[0090] Melting point: 140-142° C.

[0091] NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H), 3.63 (s, 2H). 7.22-7.48 (m, 7H), 7.74 (m, 1H), 8.01 (s, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.30 (s, 1H).

Example 4 Preparation of N-(3-methylcarbamoylphenyl)-1-phenylcyclopentanecarboxamide (Compound No. 11 in Table 1)

[0092] Melting point: 147° C.

[0093] IR (KBr, cm⁻¹): 3339, 3275, 1638, 1586, 1557, 1528.

[0094] NMR (DMSO-d₆, δ): 1.67 (m, 4H), 1.94 (m, 2H), 2.65 (m, 2H), 2.75 (d, J=4.5 Hz, 3H), 7.20-7.60 (m, 7H), 7.76 (d, J=7.2 Hz, 1H), 7.98 (s, 1H), 8.33 (d, J=4.5 Hz, 1H), 9.32 (s, 1H).

Example 5 Preparation of N-(3-methylcarbamoylphenyl)-3-fluorophenylacetamide (Compound No. 14 in Table 1)

[0095] Melting point: 147-148° C.

[0096] IR (KBr, cm⁻¹): 3314, 1661, 1636, 1587, 1530.

[0097] NMR (DMSO-d₆, δ): 2.76 (d, J=4.2 Hz, 3H), 3.69(s, 2H), 7.08 (dd, J=5.7 Hz, 5.7 Hz, 1H), 7.14 (d, J=7.5 Hz, 2H), 7.38 (m, 2H), 7.47 (d, J=8.1 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 8.02 (s, 1H), 8.35 (d, J=4.2 Hz, 1H), 10.30 (s, 1H).

Example 6 Preparation of N-(3-methylcarbamoylphenyl-4-fluorophenylacetamide (Compound No. 15 in Table 1)

[0098] Melting point: 155-156° C.

[0099] IR (KBr, cm⁻¹): 3293, 1657, 1634, 1588, 1535, 1512.

[0100] NMR (DMSO-d₆, δ): 2.76 (d, J=3.9 Hz, 3H), 3.65 (s, 2H), 7.15 (dd, J=9.0 Hz, 9.0 Hz, 2H), 7.25-7.41 (m, 3H), 7.47 (d, J=7.5 Hz, 1H), 7.75 (d, J=8.1 Hz, 1H). 8.02 (s, 1H), 8.35 (d, J=3.9 Hz, 1H, 10.28 (s, 1H).

Example 7 Preparation of N-(3-methylcarbamoylphenyl)-2-chlorophenylacetamide (Compound No. 16 in Table 1)

[0101] Melting point: 211-212° C.

[0102] IR (KBr, cm⁻¹): 3268, 1659, 1642, 1586, 1535.

[0103] NMR (DMSO-d₆, δ): 2.77 (d, J=3.6 Hz, 3H), 3.85 (s, 2H), 7.25-7.55 (m, 6H), 7.74 (d, J=7.5 Hz, 1H), 8.04 (s, 1H), 8.36 (d, J=3.6 Hz, 1H), 10.34 (s, 1H).

Example 8 Preparation of N-(3-methylcarbamoylphenyl)-4-chlorophenylacetamide (Compound No. 18 in Table 1)

[0104] Melting point: 163-164° C.

[0105] IR (KBr, cm⁻¹): 3279, 1663, 1640, 1588, 1535.

[0106] NMR (DMSO-d₆, δ): 2.76 (d, J=3.9 Hz, 3H), 3.66 (s, 2H), 7.35-7.42 (m, 5H), 7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.02 (dd, J=1.5 Hz, 1.5 Hz, 1H), 8.36 (d, J=3.9 Hz, 1H), 10.30 (s, 1H.

Example 9 Preparation of N-(3-carbamoylphenyl)-3-bromophenylacetamide (Compound No. 20 in Table 1)

[0107] Melting point: 202° C.

[0108] IR (KBr, cm⁻¹): 3378, 3295, 1659, 1624, 1586, 1534.

[0109] NMR (DMSO-d₆, δ): 3.67 (s, 2H), 7.20-7.60 (m, 7H), 7.76 (d, J=9.3 Hz, 1H), 7.94 (s, 1H), 8.03(s, 1H, 10.33 (s, 1H).

Example 10 Preparation of N-(3-methylcarbamoylphenyl)-3-bromophenylacetamide (Compound No. 22 in Table 1)

[0110] Melting point: 176-178° C.

[0111] IR (KBr, cm⁻¹): 3324, 3254, 1642, 1591, 1554.

[0112] NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.68 (s, 2H), 7.27-7.41 (m, 3H), 7.45-7.50 (m, 2H), 7.56 (s, 1H), 7.75 (d, J=8.0 Hz, 1H), 8.03 (s, 1H), 8.42 (d, J=4.5 Hz, 1H), 10.35 (s, 1H).

Example 11 Preparation of N-(3-dimethylcarbamoylphenyl)-3-bromophenylacetamide (Compound No. 23 in Table 1)

[0113] Melting point: 119-120° C.

[0114] IR (KBr, cm⁻¹): 1678, 1613, 1588, 1557.

[0115] NMR (DMSO-d₆, δ): 2.90 (s, 3H), 2.96 (s, 8H), 3.68 (s, 2H), 7.06 (d, J=7.8 Hz, 1H), 725-7.41 (m, 3H), 7.47 (m, 1H), 7.53-7.60 (m, 2H), 7.68 (s, 1H), 10.30 (s, 1H).

Example 12 Preparation of N-(3-ethylcarbamoylphenyl)-3-bromophenylacetamide (Compound No. 24 in Table 1)

[0116] Melting point: 155° C.

[0117] IR (KBr, cm⁻¹): 3329, 3268, 1665, 1640, 1549.

[0118] NMR (DMSO-d₆, δ): 1.11 (t, J=6.9 Hz, 3H), 3.29 m, 2H), 3.67 (s, 2H), 7.20-7.40 (m, 3H), 7.47 (d, J=8.1 Hz, 1H), 7.49 (d, J=8.1 Hz, 1H), 7.56 (s, 1H), 7.75 (d, J=8.4 Hz, 1H), 8.00 (s, 1H), 8.41 (t, J=5.1 Hz, 1H), 10.32 (s, 1H).

Example 13 Preparation of N-(3-(2hydroxyethyl)carbamoylphenyl)-3-bromophenylacetamide (Compound No. 28 in Table 1)

[0119] Melting point: 202° C.

[0120] IR (KBr, cm⁻¹): 3407, 3358, 3279, 1671, 1640, 1589, 1539.

[0121] NMR (DMSO-d₆, δ): 3.26 (m, 2H), 3.47 (m, 2H), 3.65 (s 2H), 4.67 (t, J=5.7 Hz, 1H), 7.20-7.60 (m, 6H), 7.73 (d, J=7.2 Hz, 1H), 7.99 (s, 1H), 8.32 (m, 1H), 10.28 (s, 1H).

Example 14 Preparation of N-(3-hydroxycarbamoylphenyl)-3-bromophenylacetamide (Compound No. 29 in Table 1)

[0122] Melting point: 184-186° C. (decomposition)

[0123] IR (KBr, cm⁻¹): 3314, 3231, 1663, 1632, 1582, 1535.

[0124] NMR (DMSO-d₆, δ): 3.68 (s 2H:, 7.25-7.60 (m, 6H), 7.75 (d, J=6.9 Hz, 1H), 7.98 (s, 1H), 9.01 (s, 1H, 10.33 (s, 1H), 11.12 (s, 1H).

Example 15 Preparation of N-(methoxycarbamoylphenyl)-3-bromophenylacetamide (Compound No. 30 in Table 1)

[0125] Melting point: 166° C.

[0126] IR (KBr, cm⁻¹): 3299, 3187, 1659, 1611, 1595, 1560.

[0127] NMR (DMSO-d₆, δ): 3.69 (s, 5H), 7.22-7.60 (m, 6H), 7.77 (s, 1H, 8.00 (s, 1H), 10.37 (s, 1H), 11.69 (s, 1H).

Example 16 Preparation of N-(3-methylcarbamoylphenyl)-4-bromophenylacetamide (Compound No. 33 in Table 1)

[0128] Melting point: 165-166° C.

[0129] IR (KBr, cm⁻¹): 3283, 1665, 1642, 1588, 1534.

[0130] NMR (DMSO-d₆, δ): 2.77 (d, J=4.5 Hz, 3H), 3.64 (s, 2H), 7.23-7.40 (m, 3H), 7.40-7.58 (m, 3H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.30 (s, 1H).

Example 17 Preparation of N-(3-methylcarbamoylphenyl)-3-methylphenylacetamide (Compound No. 42 in Table 1)

[0131] Melting point: 131° C.

[0132] IR (KBr, cm⁻¹): 3299, 1659, 1634, 1586, 1530.

[0133] NMR (DMSO-d₆, δ): 2.29 (s, 3H), 2.76 (d, J=4.5 Hz, 3H), 3.60 (s, 2H), 7.06 (d, J=6.9 Hz, 1H, 7.09-7.22 (m, 3H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.02 (s, 1H), 8.35 (d, J=4.5 Hz, 1H), 10.26 (s, 1H).

Example 18 Preparation of N-(3-methylcarbamoylphenyl)-4-methylphenylacetamide (Compound No. 43 in Table 1)

[0134] Melting point: 174-175° C.

[0135] IR (KBr, cm⁻¹): 3339, 3296, 1659, 1639, 1586, 1528.

[0136] NMR (DMSO-d₆, δ): 2.27 (s, 3H), 2.76 (d, J=4.5 Hz, 3H), 3.59 (s, 2H), 7.12 (d, J=8.1 Hz, 2H), 7.22 (d, J=8.1 Hz, 2H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.35 (d, J=1.5 Hz, 1H), 10.24 (s, 1H).

Example 19 Preparation of N-(3-methylcarbamoylphenyl)-3-methoxyphenylacetamide (Compound No. 59 in Table 1)

[0137] Melting point: 104-106° C.

[0138] NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.60 (s, 2H), 3.73 (s, 3H), 6.81 (m, 1H), 6.89-6.92 (m, 2H), 7.23 (m, 2H, 7.36 (m, 1H), 7.47 (m, 1H), 7.76 (m, 1H), 8.02 (s, 1H), 8.38 (m, 1H), 10.28 (s, 1H).

Example 20 Preparation of N-(3-methylcarbamoylphenyl)-4-methoxyphenylacetamide (Compound No. 60 in Table 1)

[0139] Melting point: 155-157° C.

[0140] NMR (DMSO-₆, δ): 2.75 (d, J=4.5 Hz, 3H), 3.55 (s, 2H), 3.71 (s, 3H), 6.88 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.8 Hz, 2H), 7.35 (m, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 8.00 (s, 1H), 8.37 (m, 1H), 10.24 (s, 1H).

Example 21 Preparation of N-(3-methylcarbamoylphenyl)-3,4-dimethoxyphenylacetamide (Compound No. 61 in Table 1)

[0141] NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H), 3.55 (s, 2H), 3.71 (s, 3H), 3.73 (s, 3H), 6.82-6.94 (m, 3H), 7.35 (m, 1H), 7.46 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.00 (s, 1H), 8.37 (m, 1H), 10.22 (s, 1H).

Example 22 Preparation of N-(3-methylcarbamoylphenyl)-3,5-dimethoxyphenylacetamide (Compound No. 62 in Table 1)

[0142] Melting point: 146-147° C.

[0143] IR (KBr, cm⁻¹): 3341, 3246, 1667, 1638, 1589, 1547.

[0144] NMR (DMSO-d₆, δ): 2.76 (d, J=4.2 Hz, 3H), 3.56 (s, 2H), 3.73 (s, 6H), 6.39 (s, 1H), 6.51 (s, 2H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.35 (d, J=4.2 Hz, 1H), 10.23 (s, 1H).

Example 23 Preparation of N-(3-methylcarbamoylphenyl)-3,4,5-trimethoxyphenylacetamide (Compound No. 63 in Table 1)

[0145] Melting point; 81-82° C.

[0146] IR (KBr, cm⁻¹): 3304, 1642, 1589, 1554, 1508.

[0147] NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.57 (s, 2H), 3.63 (s, 3H), 3.77 (s, 6H), 6.66 (s, 2H), 7.39 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 8.03 (s, 1H), 8.37 (d, J=4.5 Hz, 1H, 10.23 (s, 1H).

Example 24 Preparation of N-(3-methylcarbamoylphenyl)-3-benzyloxyphenylacetamide (Compound No. 68 in Table 1)

[0148] Melting point; 150° C.

[0149] IR (KBr, cm⁻¹): 3302, 1661, 1634, 1586, 1530.

[0150] NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.61 (s, 2H), 5.09 (s, 2H), 6.91 (dd, J=7.81 Hz, 7.8 Hz, 2H), 7.01 (s, 1H), 7.27 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.25-7.52 (m, 7H), 7.74 (d, J=7.8 Hz, 1H), 8.02 (s, 1H), 8.36 (d, J=4.5 Hz, 1H), 10.27 (s, 1H).

Example 25 Preparation of N-(3-carbamoylphenyl)-3-hydroxyphenylacetamide (Compound No 71 in Table 1)

[0151] Melting point; 188-189° C.

[0152] NMR (DMSO-d₆, δ): 3.52 (s, 2H), 6.62 (m, 1H), 6.72-6.75 (m, 2H), 7.08 (m, 1H), 7.32-7.37 (m, 2H), 7.51 (d, J=6.9 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 7.92 (1H), 8.02 (s, 1H), 9.34 (s, 1H), 10.25 (s, 1H).

Example 26 Preparation of N-(3-methylcarbamoylphenyl)-3-hydroxyphenylacetamide (Compound No. 72 in Table 1)

[0153] Melting point; 163° C.

[0154] IR (KBr, cm⁻¹): 3333, 3293, 1676, 1640, 1588, 1562.

[0155] NMR (DMSO-d₆, δ): 2.74 (d, J=4.2 Hz, 3H), 3.53 (s, 2H), 6.61 (d, J=7.2 Hz, 1H), 6.72 (d, J=7.2 Hz, 1H), 6.74 (s, 1H), 7.08 (dd, J=7.2 Hz, 7.2 Hz, 1H), 7.34 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.73 (d, J=7.81 Hz, 1H), 7.80 (s, 1H), 8.34 (d, J=4.2 Hz, 1H), 9.30 (s, 1H), 10.22 (s, 1H).

Example 27 Preparation of N-(3-methylcarbamoylphenyl)-4-hydroxyphenylacetamide (Compound No. 73 in Table 1)

[0156] Melting point; 195-196° C.

[0157] IR (KBr, cm⁻¹): 3393, 3283, 1661, 1638, 1541, 1518.

[0158] NMR (DMSO-d₆, δ): 2.73 (d, J=4.5 Hz, 3H), 3.48 (s, 2H), 6.68 (d, J=8.4 Hz, 2H), 7.10 (d, J=8.4 Hz, 2H), 7.33 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.43 (d, J=8.71 Hz, 1H), 7.72 (d, J=7.8 Hz, 1H), 7.98 (s, 1H), 8.32 (d, J=4.5 Hz, 1H), 9.20 (s, 1H), 10.14 (s, 1H).

Example 28 Preparation of N-(3-methylcarbamoylphenyl)-3-methylcarbamoylphenyl)-3-nitrophenylacetamide (Compound No. 74 in Table 1)

[0159] Melting point 139° C.

[0160] IR (KBr, cm⁻¹): 3322, 3250, 1665, 1640, 1666, 1524.

[0161] NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.86 (s, 2H, 7.37 (dd, J=7.8 Hz, 7.8, Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.64 (dd, J=8.1 Hz, 8.1 Hz, 1H), 7.75 (d, J=8.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 8.03 (s, 1H), 8.13 (d, J=8.1 Hz, 1H), 8.24 (s, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.39 (s, 1H).

Example 29 Preparation of N-(3-methylcarbamoylphenyl)-4-nitrophenylacetamide (Compound No. 75 in Table 1)

[0162] Melting point: 148-151° C.

[0163] IR (KBr, cm⁻¹): 3277, 1663, 1640, 1588, 1522.

[0164] NMR (DMSO-d₆, δ): 2.74 (d, J=4.2 Hz, 3H), 3.83 (2H), 7.35 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (m, 1H), 7.60 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.4 Hz, 1H), 8.00 (s, 1H), 8.19 (d, J=8.7 Hz, 2H, 8.33 (d, J=4.2 Hz, 1H, 10.36 (s, 1H).

Example 30 Preparation of N-(3-methylcarbamoylphenyl)-1-naphthylacetamide (Compound No. 113 in Table 1)

[0165] Melting point; 201-202° C.

[0166] IR (KBr, cm⁻¹): 3274, 1657, 1640, 1588, 1532.

[0167] NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H), 4.16 (, 2H), 7.36 (dd, J=8.1 Hz, 8.1 Hz, 1H), 7.40-7.60 (m, 5H), 7.74 (d, J=7.8 Hz, 1H), 7.84 (d, J=7.8 Hz, 1H), 7.97 (d, J=7.8 Hz, 1H), 8.03 (s, 1H), 8.35 (d, J=7.8 Hz, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.44 (s, 1H).

Example 31 Preparation of N-(3-methylcarbamoylphenyl)-2-naphthylacetamide (Compound No. 114 in Table 1)

[0168] Melting point: 175-176° C.

[0169] IR (KBr, cm⁻¹): 3393, 1655, 1634, 1588, 1530.

[0170] NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.83 (s, 2H), 7.37 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.40-7.55 (m, 4H), 7.77 (d, J=8.4 Hz, 1H), 7.81-7.96 (m, 4H), 8.04 (s, 1H), 8.36 (d, J=4.1 Hz, 1H), 10.37 (s, 1H).

Example 32 Preparation of N-(3-methylcarbamoylphenyl)-3-indolylacetamide (Compound No. 140 in Table 1)

[0171] Melting point: 168-169° C.

[0172] IR (KBr, cm⁻¹): 3382, 3287, 1655, 1636, 1588, 1555, 1528.

[0173] NMR (DMSO-d₆, δ): 2.73 (d, J=4.5 Hz, 3H), 3.72 (s, 2H), 6.96 (dd, J=7.5 Hz, 7.5 Hz, 1H), 7.05 (dd, J=7.81 Hz, 7.8 Hz, 1H), 7.24 (s, 1H), 7.27-7.38 (m, 2H), 7.43 (d, J=7.8 Hz, 1H), 7.59 (d, J=7.8 Hz, 1H), 7.75 (d, J=8.7 Hz, 1H), 8.00 (s, 1H), 8.32 (d, J=4.5 Hz, 1H), 10.18 (s, 1H), 10.88 (s, 1H).

Example 33 Preparation of N-(3-methylcarbamoylphenyl)-3-benzothienylacetamide (Compound No. 146 in Table 1)

[0174] Melting point; 194° C.

[0175] IR (KBr, cm⁻¹): 3285, 1663, 1636, 1588, 1532.

[0176] NMR (DMSO-d₆, δ): 2.75 (d, J=4.2 Hz, 3H), 3.94 (s, 2H), 7.32-7.53 (4H), 7.61 (s, 1H), 7.76 (d, J=6.9 Hz, 1H), 7.91 (d, J=7.2 Hz, 1H), 7.98 (d, J=7.2 Hz, 1H), 8.04 (s, 1H), 8.35 (d, J=4.2 Hz, 1H), 10.40 (s, 1H).

Example 34 Preparation of N-(3-methylcarbamoylphenyl)-4-benzothienylacetamide (Compound No. 148 in Table 1)

[0177] Melting point: 192° C.

[0178] IR (KBr, cm⁻¹): 3295, 1676, 1632, 1595, 1559.

[0179] NMR (DMSO-d₆, δ): 2.76 (d, J=4.2 Hz, 3H), 4.03 (s, 2H), 7.30-7.41 (m, 3H), 7.47 (d, J=7.8 Hz, 1H), 7.65 (d, J=5.4 Hz, 1H), 7.75 (d, J=6.3 Hz, 1H), 7.77 (d, J=5.4 Hz, 1H), 7.91 (m, 1H), 8.02 (s, 1H), 8.35 (d, J=4.2 Hz, 1H), 10.39 (s, 1H).

Example 35 Preparation of N-(3-methylcarbamoylphenyl)-2,2-dimethyl-2,3-dihydro-5-benzofuranylacetamide (Compound No. 157 in Table 1)

[0180] Melting point; 92-93° C.

[0181] IR (KBr, cm⁻¹): 3289, 1665, 1611, 1589, 1555

[0182] NMR (DMSO-₆, δ): 1.39 (s, 6H), 1.53 (s, 1H), 2.75 (d, J=4.5 Hz, 3H), 2.99 (s, 2H), 6.65 (d, J=8.4 Hz, 1H), 7.05 (d, J=8.1 Hz, 1H), 7.18 (s, 1H), 7.34 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (d, J=7.5 Hz, 1H), 7.80 (d, J=7.8 Hz, 1H), 8.02 (s, 1H), 8.33 (d, J=4.5 Hz, 1H, 9.18 (s, 1H).

Example 36 Preparation of N-(3-methylcarbamoylphenyl)-3,4-methylenedioxyphenyl-acetamide (Compound No. 159 in Table 1)

[0183] Melting point: 174-175° C.

[0184] IR (KBr, cm⁻¹): 3337, 3291, 1659, 1634, 1586, 1530, 1505.

[0185] NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.55 (s, 2H), 5.98 (s, 2H), 6.74-6.93 (m, 3H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.35 (d, J=4.5 Hz, 1H), 10.20 (s, 1H).

Example 37 Preparation of N-(3-methylcarbamoylphenyl)phenoxyacetamide (Compound No. 176 in Table 1)

[0186] Melting point: 131° C.

[0187] IR (KBR, cm⁻¹): 3378, 3283, 1669, 1640, 1588, 1535.

[0188] NMR DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H), 4.69 (s, 2H), 6.63-7.01 (m, 3H), 7.22-7.40 (m, 3H), 7.60 (d, J=7.8 Hz, 1H), 7.77 (d, J=7.8 Hz, 1H), 8.05 (s, 1H), 8.36 (d, J=4.5 Hz, 1H), 10.18 (s, 1H.

Example 38 Preparation of N-(3-methylcarbamoylphenyl)-2-chlorophenoxyacetamide (Compound No. 177 in Table 1)

[0189] Melting point: 172-173° C.

[0190] IR KBr, cm⁻¹): 3385, 3297, 1688, 1640, 1591, 1549.

[0191] NMR (DMSO-d₆, δ): 2.77 (d, J=4.5 Hz, 3H), 4.85 (s, 2H), 6.99 (dd, J=7.5 Hz, 7.5 Hz, 1H), 7.08 (d, J=8.1 Hz, 1H), 7.30 (dd, J=7.5 Hz, 7.5 Hz, 1H), 7.38-7.60 (m, 3H), 7.76 (d, J=8.4 Hz, 1H), 8.06 (s, 1H), 8.42 (d, J=4.5 Hz, 1H), 10.31 (s, 1H).

Example 39 Preparation of N-(3-methylcarbamoylphenyl)-2-methylphenoxyacetamide (Compound No. 183 in Table 1)

[0192] Melting point: 148° C.

[0193] IR (KBr, cm⁻¹): 3399, 3285, 1696, 1640, 1547.

[0194] NMR (DMSO-d₆, δ): 2.24 (s, 3H), 2.75 (d, J=4.5 Hz, 3H), 4.70 (s, 2H), 6.80-6.90 (m, 2H), 7.07-7.19 (m, 2H), 7.37 (dd, J=8.1 Hz, 7.8 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.75 (d, J=8.1 Hz, 1H), 8.05 (s, 1H), 8.35 (d, J=4.5 Hz, 1H), 10.14 (s, 1H).

Example 40 Preparation of N-(3-methylcarbamoylphenyl)-2-methoxyphenoxyacetamide (Compound No. 187 in Table 1)

[0195] Melting point: 133° C.

[0196] IR (KBr, cm⁻¹): 3385, 3268, 1690, 1638, 1591, 1547.

[0197] NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.79 (s, 3H), 4.66 (s, 2H), 6.82-7.02 (m, 4H), 7.38 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H, 8.05 (s, 1H), 8.38 (d, J=4.5 Hz, 1H), 10.18 (s, 1H).

Example 41 Preparation of N-(3-methylcarbamoylphenyl)-1-naphthyloxyacetamide (Compound No. 191 in Table 1)

[0198] Melting point: 194° C.

[0199] IR (KBr, cm⁻¹): 3405, 3304, 1696, 1638, 1541.

[0200] NMR (DMSO-d₆, δ): 2.75 (d, J=4.2 Hz, 3H), 4.92 (s, 2H), 6.92 (d, J=7.8 Hz, 1H, 7.33-7.62 (m, 6H), 7.79 (d, J=8.1 Hz, 1H), 7.88 (m, 1H), 8.08 (s, 1H), 8.31 (m, 1H), 8.41 (d, J=4.2 Hz, 1H), 10.36 (s, 1H).

Example 42 Preparation of N-(3-methylcarbamoylphenyl)-2-naphthyloxyacetamide (Compound No. 192 in Table 1)

[0201] Melting point: 174° C.

[0202] IR (KBr, cm⁻¹): 3382, 3275, 1672, 1638, 1588, 1557, 1534.

[0203] NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H), 4.82(s, 2H), 7.22-7.58 (m, 6H), 7.78-7.95 (m, 1H), 8.09 (s, 1H), 8.40 (d, J=4.5 Hz, 1H), 10.28 (s, 1H).

Example 43 Preparation of N-(3-methylcarbamoylphenyl)-2,3-dichlorophenoxyacetamide (Compound No. 204 in Table 1)

[0204] Melting point: 192-193° C.

[0205] IR (KBr, cm⁻¹): 3385, 3291, 1692, 1644, 1547.

[0206] NMR (DMSO-d₆, δ): 2.77 (d, J=4.5 Hz, 3H), 4.91 (s, 2H), 7.08 (d, J=8.1 Hz, 1H), 7.20-7.45 (m, 3H), 7.52 (d, J=7.8 Hz, 1H), 7.74 (d, J=8.7 Hz, 1H), 8.05 (s, 1H), 8.42 (d, J=4.5 Hz, 1H), 10.34 (s, 1H).

Example 44 Preparation of N-(3-methylcarbamoylphenyl)-2-methyl-1-naphthylacetamide (Compound No. 216 in Table 1)

[0207] Melting point: 230-231° C.

[0208] IR (KBr, cm⁻¹): 3299, 3071, 1684, 1638, 1589, 1560.

[0209] NMR (DMSO-d₆, δ): 2.50 (s, 3H), 2.73 (d, J=4.5 Hz, 3H), 4.21 (s, 2H), 7.22-7.55 (m, 5H), 7.65-7.78 (m, 2H), 7.85 (d, J=7.8 Hz, 1H, 8.01-8.15 (m, 2H), 8.36 (d, J=4.5 Hz, 1H), 10.50 (s, 1H).

Example 45 Preparation of N-(3-methylcarbamoylphenyl)-2-hydroxy-1-naphthylacetamide (Compound No. 219 in Table 1)

[0210] Melting point: 229-230° C.

[0211] IR (KBr, cm⁻¹): 3310, 1686, 1613, 1582, 1561.

[0212] NMR (DMSO-d₆, δ): 2.75 (d, J=4.2 Hz, 3H), 4.11 (s, 2H), 7.19 (d, J=9.0 Hz, 1H), 7.20-7.50 (m, 4H), 7.66-7.82 (m, 3H), 7.87 (d, J=8.4 Hz, 1H), 8.04 (s, 1H), 8.37 (d, J=4.5 Hz, 9.79 (s, 1H), 10.32 (s, 1H).

Example 46 Preparation of N-(3-methylcarbamoylphenyl)-3-phenylpropionamide (Compound No. 233 in Table 1)

[0213] Melting point: 142-143° C.

[0214] IR (KBr, cm⁻¹): 3295, 1657, 1613, 1593, 1545.

[0215] NMR (DMSO-d₆, δ): 2.62 (t, J=7.8 Hz, 2H), 2.75 (d, J=4.5 Hz, 3H), 2.90 (t, J=7.8 Hz, 2H), 7.10-7.40 (m, 6H), 7.44 (d, J=7.5 Hz, 1H), 7.72 (d, J=7.5 Hz, 1H), 7.99 (s, 1H), 8.33 (d, J=4.5 Hz, 1H), 10.00 (s, 1H).

Example 47 Preparation of N-(3-methylcarbamoylphenyl)-3-(2-methylphenyl)propionamide (Compound No. 240 in Table 1)

[0216] Melting point: 131° C.

[0217] IR (KBr, cm⁻¹): 3289, 1674, 1640, 1555.

[0218] NMR (DMSO-d₆, δ): 2.29 (s, 3H), 2.57 (t, J=7.8 Hz, 2H, 2.75 (d, J=4.2 Hz, 3H), 2.88 (t, J=7.8 Hz, 2H), 7.02-7.18 (m, 4H), 7.34 (dd, J=7.8 Hz, 7.2 Hz, 1H), 7.44 (d, J=7.2 Hz, 1H), 7.73 (d, J=7.8 Hz, 1H), 7.98 (s, 1H), 8.33 (d, J=4.2 Hz, 1H), 10.01 (s, 1H)

Example 48 Preparation of N-(3-methylcarbamoylphenyl)-3-(4-hydroxyphenyl)propionamide (Compound No. 245 in Table 1)

[0219] Melting point: 158° C.

[0220] IR (KBr, cm⁻¹): 3424, 3285, 1647, 1553.

[0221] NMR (DMSO-d₆, δ): 2.54 (t, J=7.8 Hz, 2H), 2.74 (d, J=4.2 Hz, 3I), 2.78 (t, J=7.8 Hz, 2H), 6.64 (d, J=8.1 Hz, 2H), 7.01 (d, J=8.1 Hz, 2H), 7.33 (dd, J=8.1 Hz, 7.5 Hz, 1H), 7.43 (d, J=7.5 Hz, 1H), 7.71 (d, J=8.1 Hz, 1H), 7.98 (s, 1H), 8.32 (d, J=4.2 Hz, 1H), 9.10 (s, 1H), 9.97 (s, 1H).

Example 49 Preparation of N-(3-methylcarbamoylphenyl)-3-(2-methoxyphenyl)propionamide (Compound No. 246 in Table 1)

[0222] Melting point: 150° C.

[0223] IR (KBr, cm⁻¹): 3297, 1658, 1644, 1550.

[0224] NMR (DMSO-d₆, δ): 2.56 (t, J=7.2 Hz, 2H), 275 (d, J=3.9 Hz, 3H), 2.85 (t, J=7.2 Hz, 2H), 3.78 (s, 3H), 6.84 (dd, J=7.5 Hz, 7.5 Hz, 1H), 6.93 (d, J=7.5 Hz, 1H), 7.05-7.20 (m, 2H), 7.26 (dd, J=8.1 Hz, 8.1 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.99 (s, 1H), 8.38 (d, J=3.9 Hz, 1H), 9.67 (s, 1H).

Example 50 Preparation of N-(3-methylcarbamoylphenyl)-3-(4-methoxyphenyl)propionamide (Compound No. 248 in Table 1)

[0225] Melting point: 151-152° C.

[0226] IR (KBr, cm⁻¹): 3289, 1669, 1634, 1613, 1557, 1514.

[0227] NMR (DMSO-d₆, δ): 2.57 (t, J=7.5 Hz, 2H), 2.77 (d, J=4.2 Hz, 3H), 2.85 (t, J=7.5 Hz, 2H), 3.71 (s, 3H), 6.84 (d, J=8.1 Hz, 2H), 7.16 (d, J=8.1 Hz, 2H), 7.35 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.5 Hz, 1H), 8.01 (s, 1H), 8.34 (d, J=4.2 Hz, 1H), 10.00 (s, 1H).

Example 51 Preparation of N′-methyl-3-(4-methylbenzyloxycarbonylamino)benzamide (Compound No.51 in Table 2)

[0228] 4-Methylbenzylalcohol (307 mg) and di(N-succinimidyl)carbonate (966 mg) were dissolved in methylene chloride (20 ml), and triethylamine (0.70 ml) was added to the solution. After stirring for 4 hours at room temperature, water was added and an aqueous layer was extracted with methylene chloride. The extracted aqueous layer was successively washed with an aqueous saturated sodium chloride solution, an aqueous saturated sodium bicarbonate solution, an aqueous saturated sodium chloride solution, 2N hydrochloric acid, and an aqueous saturated sodium chloride solution, and dried over magnesium sulfate. After removing magnesium sulfate by filtration, the filtrate was concentrated to obtain N-(4-methylbenzyloxycarbonyloxy)succinate imide (664 mg) as an intermediate.

[0229] N-(4-methylbenzyloxycarbonyloxy)succinate imide (610 mg of the above-obtained product) was dissolved in dimethylformamide (2 ml), and 3-aminobenzoylmethyamide (313 mg) and triethylamine (0.32 ml) were added thereto. After stirring overnight at room temperature, the obtained insoluble material was added to water (15 ml) while the insoluble products are being filtered. The crystals obtained from filtrate was filtered and washed with water to obtain crude crystals. The crude crystals were dried and added to ethyl acetate (8 ml), and was heated under reflux for 10 minutes. The mixture was cooled to room temperature, and the crystals were collected by filtration and washed with ethyl acetate to obtain the desired compound (167 mg, yield 27%).

[0230] Melting Point: 167-168° C.

[0231] IR(KBr,cm⁻¹): 3322,1738,1622,1557.

[0232] NMR(DMSO-d₆, δ): 2.28(s,3H), 2.74(d,J=4.6 Hz,3H), 5.09(s,2H), 7.17(d,J=7.9 Hz,2H), 7.23-7.42(m,4H), 7.54(d,J=6.5 Hz,1H), 7.91(s, 1H), 8.31(d,J=4.6 Hz, 1H), 9.82(s,1H).

[0233] In similar manners to the method of Example 51, compounds of Example 52-68 and Example 72 were prepared. Their physicochemical properties are set out below.

Example 52 Preparation of N′-methyl-3-(2-fluorobenzyloxycarbonylamino)benzamide (Compound No.17 in Table 2)

[0234] Melting Point: 189-190° C.

[0235] IR(KBr,cm⁻¹): 3341,3291,1730,1622,1557.

[0236] NMR(DMSO-d₆, δ): 2.76(d,J=4.2 Hz,3H), 5.22(s,2H, 7.20-7.45(m,5H), 7.50-7.60(m,2H), 7.94(s,1H), 8.36(d,J=4.2 Hz,1H), 9.93(s,1H).

Example 53 Preparation of N′-methyl-3-(4-fluorobenzyloxycarbonylamino)benzamide (Compound No.21 in Table 2)

[0237] Melting Point; 153° C.

[0238] IR(KBr,cm⁻¹): 3304,1732,1626,1613,1559.

[0239] NMR(DMSO-d₆, δ): 2.76(d, J=3.4 Hz,3H), 5.15(s,2H), 7.23(dd,J=8.6 Hz,8.6 Hz,2H), 7.35(dd,J=7.7 Hz,7.4 Hz, 1H), 7.42(d,J=7.4 Hz,1H), 7.49(dd,J=8.6 Hz,8.6 Hz,2H), 7.57(d,J=7.7 Hz, 1H), 7.94(s, 1H), 8.36(d,J=3.4 Hz, 1H), 9.90(s, 1H.

Example 54 Preparation of N′-methyl-3-(2-chlorobenzyloxycarbonylamino)benzamide (Compound No.23 in Table 2)

[0240] Melting Point: 168° C.

[0241] IR(KBr,cm⁻¹): 3329,3289,1728,1622,1559.

[0242] NMR(DMSO-d₆, δ): 2.74(d,J=4.4 Hz,3H, 5.23(s,2), 7.27-7.43(m,4H), 7.43-7.60(m,3H), 7.93(s, 1H), 8.30(d,J=4.4 Hz,1H), 9.94(s,1H).

Example 55 Preparation of N′-methyl-3-(4-chlorobenzyloxycarbonylamino)benzamide (Compound No.27 in Table 2)

[0243] Melting Point: 155-156° C.

[0244] IR(KBr,cm⁻¹): 3351,3299,1734,1624,1557.

[0245] NMR(DMSO-d₆, δ): 2.74(d,J=4.5 Hz,3H), 5.14(s,2H), 7.25-7.43(m,6H), 7.55(d,J=8.3 Hz,1H), 7.91(s,1H), 8.32(d,J=4.5 Hz,1H), 9.88(s,1H).

Example 56 Preparation of N′-methyl-3-(2,3-dichlorobenzyloxycarbonylamino)benzamide (Compound No.29 in Table 2)

[0246] Melting Point: 167-168° C.

[0247] IR(KBr,cm⁻¹): 3401,3258,1744,1711,1649,1561.

[0248] NMR(DMSO-d₆, δ): 2.74(d,J=4.4 Hz,3H), 5.26(s,2H), 7.25-7.43(m,3H), 7.50-7.60(m,2H), 7.64(d,J=8.0 Hz,1H), 7.93(s, 1H), 8.32(d,J=4.4 Hz, 1H), 9.97(s,1H).

Example 57 Preparation of N′-methyl-3-(2,6-dichlorobenzyloxycarbonylamino)benzamide (Compound No.85 in Table 2)

[0249] Melting Point: 219-220° C.

[0250] IR(KBr,cm⁻¹): 3380,3241,1717,1651,1562.

[0251] NMR(DMSO-d₆, δ): 2.74(d,J=4.3 Hz,3H), 5.35(s,2H), 7.25-7.60(m,6H), 7.92(s,1H), 8.35(d,J=4.3 Hz,1H), 9.92(s,1H).

Example 58 Preparation of N′-methyl-3-(2-bromobenzyloxycarbonylamino)benzamide (Compound No.41 in Table 2)

[0252] Melting Point: 163-164° C.

[0253] IR(KBr,cm⁻¹): 3324,1728,1622,1559.

[0254] NMR(DMSO-d₆, δ): 2.73(d,J=4.0 Hz,3H), 5.19(s,2H, 7.24-7.75(m,7H), 7.93(s,1H), 8.35(d,J=4.0 Hz,1H), 9.98(s,1H).

Example 59 Preparation of N′-methyl-3-(2-methylbenzyloxycarbonylamino)benzamide (Compound No.47 in Table 2)

[0255] Melting Point: 163° C.

[0256] IR(KBr,cm⁻¹): 3358,3312,1734,1622,1557.

[0257] NMR(DMSO-d₆, δ): 2.35(s,3H), 2.76(d,J=4.4 Hz,3H), 5.17(s,2H), 7.18-7.35(m,3H), 7.35-7.45(m,3H), 7.57(d,J=7.7 Hz,1H), 7.94(s,1H), 8.37(d,J=4.4 Hz,1H), 9.89(s,1H).

Example 60 Preparation of N′-methyl-3-(3-methylbenyloxycarbonylamino)benzamide (Compound No.49 in Table 2)

[0258] Melting Point: 155° C.

[0259] IR(KBr,cm⁻¹): 3343,3279,1736,1624,1559.

[0260] NMR(DMSO-d₆, δ): 2.32(s,3H), 2.76(d,J=4.2 Hz,3H), 5.12(s,2H), 7.10-7.45(m,6H), 7.57(d,J=8.0 Hz,1H), 7.94(s,1H), 8.36 (d,J=4.2 Hz, 1H), 9.89(s,1H).

Example 61 Preparation of N′-methyl-3-(4-isopropylbenzyloxycarbonylamino)benzamide (Compound No.57 in Table 2)

[0261] Melting Point: 189-190° C.

[0262] IR(KBr,cm⁻¹); 3380,3235,1709,1647,1561.

[0263] NMR(DMSO-d₆, δ): 1.19(d,J=6.8 Hz,6H), 2.76(d,J=3.9 Hz,3H), 2.88(m,1H), 5.12(s, 2H), 7.20-7.40(m,6H), 7.57(d,J=7.7 Hz,1H), 7.93(s,1H), 8.35(d,J=3.9 Hz,1H), 9.87(s,1H).

Example 62 Preparation of N′-methyl-3-(2-methoxybenzyloxycarbonylamino)benzamide (Compound No.61 in Table 2)

[0264] Melting Point: 173° C.

[0265] IR(KBr,cm⁻¹): 3341,3266,1726,1624,1561.

[0266] NMR(DMSO-d₆, δ): 2.76(d,J=4.0 Hz,3H), 3.82(s,3H), 5.14(s, 2H), 6.99(dd,J=7.4 Hz,7.4 Hz, 1H), 7.04(d,J=8.2 Hz,1H), 7.28-7.42(m,4H), 7.56(d,J=8.2 Hz,1H), 7.94(s,1H), 8.36(d,J=4.0 Hz, 1H), 9.89(s,1H).

Example 63 Preparation of N′-methyl-3-(4-methoxybenzyloxycarbonylamino)benzamide (Compound No.65 in Table 2)

[0267] Melting Point: 158-159° C.

[0268] IR(KBr,cm⁻¹): 3331,3295,1730,1613,1555.

[0269] NMR(DMSO-d₆, δ): 2.74(d,J=4.3 Hz,3H), 3.73(s,3H), 5.06(s,2H), 6.92(d,J=8.2 Hz,2H), 7.20-7.40(m,4H), 7.54(d,J=7.7 Hz, 1H), 7.90(s,1H), 8.30(d,J=4.3 Hz, 1H), 9.78(s,1H).

Example 64 Preparation of N′-methyl-3-(4-chloro2-nitrobenzyloxycarbonylamino)benzamide (Compound No.77 in Table 2)

[0270] Melting Point: 193° C.

[0271] IR(KBr,cm⁻¹): 3366,3248,1717,1624,1662,1537.

[0272] NMR(DMSO-d₆, δ): 2.76(d,J=3.3 Hz, 3H), 5.48(s, 2H, 7.36(dd,J=7.8 Hz,7.8 Hz, 1H), 7.44(d, J=7.8 Hz,1H), 7.58(d,J=7.8 Hz,1H), 7.77(d,J=8.1 Hz,1H), 7.90-7.98(m,2H), 8.23(s,1H), 8.35(d,J=3.3 Hz, 1H), 10.04(1H).

Example 65 Preparation of N′-methyl-3-(1-naphthylmethoxycarbonylamino)benzamide (Compound No.81 in Table 2)

[0273] Melting Point: 228-229° C.

[0274] IR(KBr,cm⁻¹): 3353,3285,1730,1626,1555.

[0275] NMR(DMSO-d₆, δ): 2.76(d,J=4.4 Hz,3H), 5.64(s,2H), 7.30-7.45(m,2H), 7.50-7.70(m,5H, 7.90-8.03(m,3H), 8.12(d,J=7.6 Hz,1H), 8.38(d,J=4.4 Hz, 1H), 9.87(s,1H).

Example 66 Preparation of N′-methyl-3-(2-naphthylmethoxycarbonylamino)benzamide (Compound No. 89 in Table 2)

[0276] Melting Point: 157-158° C.

[0277] IR(KBr,cm⁻¹): 3314,1699,1642,1589,1539.

[0278] NMR(DMSO-d₆, δ): 2.76(d,J=4.8 Hz,3H), 5.32(s,2H), 7.23-7.42(m,2H), 7.42-7.60(m,4H), 7.82-7.98(m,5H), 8.32(d,J=4.8 Hz, 1H), 9.90(s,1H).

Example 67 Preparation of N′-methyl-3-(5-fluorenylmethoxycarbonylamino)benzamide (Compound No.99 in Table 2)

[0279] Melting Point: 217° C.

[0280] IR(KBr,cm⁻¹): 3349,3289,1730,1624,1586,1557.

[0281] NMR(DMSO-d₆, δ): 2.76(d,J=4.2 Hz,3H), 4.32(d,J=6.6 Hz,1H), 4.48(d,J=6.6 Hz,2H), 7.25-7.50(m, 6H), 7.59(m,1H), 7.76(d,J=7.2 Hz,2H), 7.92(d,J=7.2 Hz,2H), 7.93(s,1H, 8.37(d,J=4.2 Hz,1H), 9.87(s,1H).

Example 68 Preparation of N′-methyl-3-(phenoxycarbonylamino)benzamide(Compound No.181 in Table 2)

[0282] Melting Point: 193° C.

[0283] IR(KBr,cm⁻¹): 3401,3268,1753,1624,1555.

[0284] NMR(DMSO-d₆, δ): 2.77(d,J=3.6 Hz,3H), 7.20-7.35(m, 3H), 7.35-7.45(m, 4H), 7.49(d,J=7.8 Hz, 1H), 7.63(s, 1H), 7.99(s,1H), 10.38(s,1H).

Example 69 Preparation of 1-(3-methylcarbamoylphenyl)-3-phenylurea(Compound No.182 in Table 2)

[0285] Phenylisocyanate (209 mg) and 3-aminobenzoylmethylamide (239 mg) were dissolved in dimethylformamide (2 ml. After starring for 6 hours at room temperature, dilute hydrochloric acid (15 ml) was added. The obtained crystals were filtered and washed with water to obtain crude crystals. The crude crystals were dried under reduced pressure and added to ethyl acetate (8 ml), and the mixture was heated under reflux for 10 minutes. The mixture was cooled to room temperature, and the crystals were collected by filtration and washed with ethyl acetate to obtain the desired compound (386 mg, yield 90%).

[0286] Melting Point: 209-210° C.

[0287] IR(KBr,cm⁻¹): 3328,3279,1699,1626,1557.

[0288] NMR(DMSO-d₆, δ): 2.75(d,J=4.1 Hz,3H), 6.95(dd,J=7.3 Hz,7.3 Hz), 7.20-7.45(m,6H), 7.57(d,J=7.7 Hz,1H, 7.86(s,1H), 8.37(d,J=4.1 Hz, 1H), 8.67(s,1H), 8.79(s, 1H).

[0289] In similar manners to the method of Example 69, compounds of Example 70 and Example 71 were prepared Their physicochemical properties are set out below.

Example 70 Preparation of 3-benzyl-1-(3-methylcarbamoylphenyl)urea(Compound No.5 in Table 2)

[0290] Melting Point: 189-190° C.

[0291] IR(KBr,cm⁻¹): 3366,3333,1640,1559.

[0292] NMR(DMSO-d₆, δ): 2.73(d,J=4.4 Hz,3H), 4.28(d,J=5.9 Hz,2H), 6.62(t,J=5.9 Hz,1H), 7.15-7.40(m,7H), 7.54(d,J=7.3 Hz, 1H), 7.79(s, 1H); 8.28(d,J=4.4 Hz, 1H), 8.66(s, 1H).

Example 71 Preparation of 3-benzyl-1-(3-methylcarbamoylphenyl)thiourea(Compound No.6 in Table 2)

[0293] Melting Point: 199° C.

[0294] IR(KBr,cm⁻¹): 3343,2246,3069,1630,1584,1528

[0295] NMR(DMSO-d₆, δ): 2.76(d,J=4.5 Hz,3H), 4.72(d,J=5.4 Hz,2H), 7.20-7.40(m,6H), 7.45-7.60(m,2H), 7.81(s,1H), 8.20(s,1H), 8.36(d,J=4.5 Hz, 1H), 9.65(s,1H).

Example 72 Preparation of N′-methyl-3-(2-(2-methyl-5-nitro-1-imidazolyl) ethoxycarbonylamino)benzamide (Compound No.233 in Table 2)

[0296] Melting Point: 207° C.

[0297] IR(KBr,cm⁻¹): 3362,1734,1636,1591,1533.

[0298] NMR(DMSO-d₆, δ): 2.48(s,3H), 2.76(d,J=4.2 Hz,3H), 4.47(t,J=4.8 Hz,2H), 1.61(t,J=4.8 Hz,2H), 7.34(dd,J=7.7 Hz,7.5 Hz,1H), 7.43(d,J=7.5 Hz,1H), 7.55(d,J=7.7 Hz,1H), 7.85(s,1H), 8.05(s,1H), 8.34(d,J=4.4 Hz,1H), 9.76(s, 1H)

Test Example 1 Measurement of anti-Helicobacter pylori activity

[0299] Brain heart infusion culture medium containing 10% fetal bovine serum (Difco) (5 ml) was taken in a test tube, and then the medium was inoculated with Helicobacter pylori strain 31A isolated from human (obtained from the Metropolitan Health Institute, Microorganism Department, First Laboratory of Bacteria). Cultivation was carried out under slightly aerobic condition (5% oxygen, 10% carbon dioxide, 85% nitrogen) at 37° C. for 48 hours with shaking.

[0300] The culture was then inoculated to brain heart infusion medium containing 10% fetal bovine serum at a ratio of 5%, and added with a test compound dissolved in 10% dimethyl sulfoxide. Cultivation was carried out under slightly aerobic condition at 37° C. for 48 hours with shaking, and then growth of Helicobacter pylori was examined. Antibacterial activity was recorded as the lowest concentration that exhibited growth inhibition (minimum inhibitory concentration: MIC). The results are shown in Tables 3 and 4. From the results shown in Tables 3 and 4, it can be understood that the compounds of the present invention have potent inhibitory activity against Helicobacter pylori. TABLE 3 Example No. (Compound No. in Table 1) MIC (μg/ml)  1 (No. 17) 0.39  3 (No. 7) 1.56  8 (No. 18) 0.78 10 (No. 22) 0.39 16 (No. 33) 0.78 17 (No. 42) 0.39 18 (No. 43) 0.39 19 (No. 59) 0.78 20 (No. 60) 0.78 22 (No. 62) 1.56 23 (No. 63) 0.78 24 (No. 68) 0.78 30 (No.113) 0.10 31 (No. 114) 0.05 32 (No. 140) 0.78 33 (No. 146) 0.10 34 (No. 148) 0.20 36 (No. 159) 0.78 38 (No. 177) 0.78 41 (No. 191) 0.10 42 (No. 192) 0.39 43 (No. 204) 0.39 44 (No. 216) 0.78 45 (No. 219) 0.78 49 (No. 246) 0.78

[0301] TABLE 4 Example No. (Compound No. in Table 2) MIC (μg/ml) 51 (No. 51) 0.10 52 (No. 17) 0.78 53 (No. 21) 0.78 54 (No. 23) 0.39 55 (No. 27) 0.20 56 (No. 29) 0.20 57 (No. 35) 0.20 58 (No. 41) 0.39 59 (No. 47) 0.39 60 (No. 49) 0.39 61 (No. 57) 0.78 62 (No. 61) 0.78 63 (No. 65) 0.78 65 (No. 81) 0.05 66 (No. 89) 0.10 70 (No. 5)  1.56

Test Example 2 Measurement of anti-Campylobacter jejuni activity

[0302] According to a similar method to that of Test Example 1, inhibitory activity of the compound of the present invention against Campylobacter jejuni was determined. As a result, MIC of the compound of Example 31 was 0.008 μg/ml. From the result, it can be understood that the compound of the present invention has potent inhibitory activity against Campylobacter jejuni.

Test Example 3 Acute toxicity test

[0303] The compound of the present invention, suspended in 0.5% CMC-Na aqueous solution, was forcibly administered orally to SD male and female rats, and symptoms of the rats were observed for seven days. As a result, each of LD₅₀ values of the compounds of Examples 30 and 31 was not lower than 2,000 mg/kg.

Formulation Examples

[0304] (1) Tablet

[0305] The following ingredients were mixed according to a conventional method, and compressed to obtain a tablet by using a conventional apparatus. Compound of Example 31 100 mg Crystalline cellulose 180 mg Corn starch 300 mg Lactose 600 mg Magnesium stearate  15 mg

[0306] (2) Soft capsule

[0307] The following ingredients were mixed according to a conventional method, and filled in a soft capsule. Compound of Example 41 100 mg Olive oil 900 mg Lecithin  60 mg

[0308] Industrial Applicability

[0309] The amide derivatives of the present invention have potent antibacterial activity against Helicobacter pylori, and therefore, they are useful as an active ingredient of medicaments. 

What is claimed is:
 1. A compound represented by the following general formula (I):

wherein X represents R¹(R²)(R³)C- where R¹ represents a C₃-C₈ cycloakyl group, an optionally substituted C₅-C₁₄ aryl group, an optionally substituted heterocyclic residue wherein the heterocyclic residue is one of furan ring, dihydrofuran ring, tetrahydrofuran ring, pyran ring, dihydropyran ring, tetrahydropyran ring, benzofuran ring, dihydrobenzofuran ring, isobenzofuran ring, chromene ring, chroman ring, isochroman ring, thiophene ring, benzothiophene ring, pyrrole ring, pyrroline ring, pyrrolidine ring, imidazole ring, imidazoline ring, imidazolidine ring, pyrazole ring, pyrazoline ring, pyrazolidine ring, triazole ring, tetrazole ring, pyridine ring, pyridineoxide ring, piperidine ring, pyrazine ring, piperazine ring, pyrimidine ring, pyridazine ring, indoline ring, indole ring, indoline ring, isoindole ring, isoindoline ring, indazole ring, benzimidazole ring, purine ring, quinolizine ring, quinoline ring, phthalazine ring, naphthylidine ring, quinoxaline ring, quinazoline ring, cinnoline ring, pteridine ring, oxazole ring, oxazolidine ring, isoxazole ring, isoxazolidine ring, thiazole ring, thiazylidine ring, isothiazole ring, isothiazolidine ring, dioxane ring, dithian ring, morpholine ring, and thiomorpholine ring, an optionally substituted C₆-C₁₄ aryloxy group, or an optionally substituted C₇-C₁₅ arylmethyl group; R² and R³ independently represent hydrogen atom or a C₁-C₅ alkyl group, or R² and R³ may combine to represent a C₂-C₇ alkylene group; or X represents R⁷-A- wherein R⁷ represents (i) a C1-C10 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group, an optionally substituted fluorenyl group or an optionally substituted heterocyclic group, (ii) an optionally substituted C6-C14 aryl group or (iii) an optionally substituted heterocyclic group, and A represents an oxygen atom or -N-R⁸ where R⁸ represents hydrogen atom or a C1-C5 alkyl group, Y represents an oxygen atom or a sulfur atom, R⁴ and R⁵ independently represent hydrogen atom or a C₁-C₅ alkyl group; and R⁶ represents hydrogen atom, a C₁-C₅ alkyl group which may optionally be substituted with a hydroxyl group, a hydroxyl group or a C₁-C₅ alkoxy group, provided that the compounds wherein R⁷ is a benzyl group, A and Y are an oxygen atom, R⁴ and R⁶ are hydrogen atom, and R⁶ is a propyl group are excluded, or a salt thereof, or a solvate thereof or a hydrate thereof.
 2. The compound according to claim 1 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁴ is hydrogen atom.
 3. The compound according to claim 1 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁵ is hydrogen atom.
 4. The compound according to claim 3 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁶ is a C₁-C₅ alkyl group.
 5. The compound according to claim 4 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁶ is methyl group.
 6. The compound according to claim 1 or a salt thereof or a solvate thereof or a hydrate thereof, wherein Y is an oxygen atom.
 7. The compound according to claim 6 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein X is R¹(R²)(R³)C-.
 8. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R² and R³ are hydrogen atoms.
 9. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R¹ is a C₆-C₁₄ aryl group which may optionally be substituted.
 10. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R¹ is a residue of a heterocyclic compound which may optionally be substituted.
 11. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R¹ is a C₆-C₁₄ aryloxy group which may optionally be substituted.
 12. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R¹ is a C₇-C₁₅ arylmethyl group which may optionally be substituted.
 13. The compound according to claim 1 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein X is R⁷-A-.
 14. The compound according to claim 13 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein A is an oxygen atom or -N-H.
 15. The compound according to claim 13 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁷ is a C1-C10 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group.
 16. The compound according to claim 15 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁷ is a C1-C5 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group.
 17. The compound according to claim 16 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁷ is a methyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group.
 18. The compound according to claim 17 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁷ is a methyl group which is substituted with an optionally substituted C6-C14 aryl group.
 19. The compound according to claim 17 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁷ is a methyl group which is substituted with an optionally substituted heterocyclic group.
 20. A compound selected from the group consisting of: N-(3-methylcarbamoylphenyl)-3-chlorophenylacetamide; N-(3-methylcarbamoylphenyl)-4-chlorophenylacetamide; N-(3-methylcarbamoylphenyl)-3-bromophenylacetamide; N-(3-methylcarbamoylphenyl)-4-bromophenylacetamide: N-(3-methylcarbamoylphenyl)-3-methylphenylacetamide; N-(3-methylcarbamoylphenyl)-4-methylphenylacetamide; N-(3-methylcarbamoylphenyl)-3-methoxyphenylacetamide; N-(3-methylcarbamoylphenyl)-4-methoxyphenylacetamide; N-(3-methylcarbamoylphenyl)-3,4,5-trimethoxyphenylacetamide; N-(3-methylcarbamoylphenyl)-3-benzyloxyphenylacetamide; N-(3-methylcarbamoylphenyl)-1-naphthylacetamide; N-(3-methylcarbamoylphenyl)-2-naphthylacetamide; N-(3-methylcarbamoylphenyl)-3-inadolylacetamide; N-(3-methylcarbamoylphenyl)-3-benzothienylacetamide; N-(3-methylcarbamoylphenyl)-4-benzothienylacetamide; N-(3-methylcarbamoylphenyl)-3,4-methylenedioxyphenylacetamide; N-(3-methylcarbamoylphenyl)-2-chlorophenoxyacetamide; N-(3-methylcarbamoylphenyl)-2,3-chlorophenoxyacetamide; N-(3-methylcarbamoylpheny)-1-naphthyloxyacetamide; N-(3-methylcarbamoylphenyl)-2-naphthyloxyacetimide; and N-(3-methylcarbamoylphenyl)-3-(2-methoxyphenyl)propionamide, or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.
 21. A compound selected from the group consisting of: N′-methyl-3-(2-chlorobenzyloxycarbonylamino)benzamide, N′-methyl-3-(4-chlorobenxyloxycarbonylamino)benzamide; N′-methyl-3-(2,3-dichlorobenzyloxycarbonylamino)benzamide; N′-methyl-3-(2,6-dichlorobenzyloxycarbonylamino)benzamide; N′-methyl-3-(2-bromobenzyloxycarbonylamino)benzamide; N′-methyl-3-(2-methylbenzyloxycarbonylamino)benzamide; N′-methyl-3(3-methylbenzyloxycarbonylamino)benzamide; N-methyl-3-(4-methylbenzyloxycarbonylamino)benzamide; N′-methyl-3-(1-naphthylmethoxycarbonylamino)benzamide; and N′-methyl-3-(2-naphthylmethoxycarbonylamino)benzamide; or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.
 22. N-(3-methylcarbamoylpheny)-1-naphthylacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.
 23. N-(3-methylcarbamoylphenyl)-2-naphthylacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.
 24. N-(3-methylcarbamoylphenyl)-3-benzothienylacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.
 25. N-(3-methylcarbamoylphenyl)-4-benzothienylacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.
 26. N-(3-methylcarbamoylphenyl)-1-naphthyloxyacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.
 27. A medicament comprising as an active ingredient a substance selected from the group consisting of a compound according to claim 1 and a salt thereof, and a solvate thereof and a hydrate thereof.
 28. The medicament according to claim 27 which is in the form of a pharmaceutical composition comprising said substance as an active ingredient and one or more pharmaceutical additives.
 29. The medicament according to claim 27 which has antibacterial activity.
 30. The medicament according to claim 29 which has antibacterial activity against a microorganism belonging to the genus Helicobacter and/or Campylobacter.
 31. The medicament according to claim 30 which has anti-Helicobacter pylori activity and/or anti-Campylobacter jejuni activity.
 32. A process for at least one of preventing and treating a digestive disease, comprising administering the medicament according claim
 27. 33. The process of claim 32, wherein the digestive disease is one of gastritis, gastric ulcer, gastric cancer, gastric malignant lymphoma, MALT lymphoma, duodenal ulcer, duodenal carcinoma, and enteritis.
 34. A process for preventing recurrence of a digestive disease, comprising administering the medicament according to claim
 27. 35. The process of claim 34, wherein the digestive disease is one of gastric ulcer and duodenal ulcer. 